SNPMiner Trials by Shray Alag


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Report for Mutation C282Y

Developed by Shray Alag, 2020.
SNP Clinical Trial Gene

There are 49 clinical trials

Clinical Trials


1 Hemochromatosis and Iron Overload Screening Study (HEIRS)

To determine the prevalence, genetic and environmental determinants, and potential clinical, personal, and societal impact of iron overload and hereditary hemochromatosis, in a multi-center, multiethnic, primary care-based sample of 100,000 adults. The study is conducted by the Division of Epidemiology and Clinical Applications of the NHLBI, the Division of Blood Diseases and Resources of the NHLBI, and the Ethical, Legal, and Social Implications (ELSI) Research Program of the NHGRI.

NCT00005541 Blood Disease Hemochromatosis Iron Overload
MeSH: Hematologic Diseases Hemochromatosis Iron Overload
HPO: Abnormality of blood and blood-forming tissues

Evidence suggests that early diagnosis and treatment can prevent disease manifestations and enable normal life expectancy The discovery of the HFE C282Y and H63D variants in the HLA gene region on chromosome 6 provides an opportunity for early and rapid genetic identification of individuals at risk for development of hereditary hemochromatosis. --- C282Y ---

In order to obtain data on the prevalence of genetic factors in a routine care population, a random subgroup of approximately 20-40 percent of the 101,000 screenees will be genotyped for known variants, such as HFE C282Y and H63D, related to iron metabolism and overload. --- C282Y ---


2 Studies of Phlebotomy Therapy in Hereditary Hemochromatosis

This study will evaluate the effectiveness of a test called MCV in guiding phlebotomy (blood drawing) therapy in patients with hemochromatosis an inherited disorder that causes too much iron to be absorbed by the intestine. The excess damages body tissues, most severely in the liver, heart, pancreas and joints. Because iron is carried in the hemoglobin of red blood cells, removing blood can effectively lower the body s iron stores. Patients with hemochromatosis undergo weekly phlebotomy treatments (1 pint per session) to deplete iron stores. This usually requires 10 to 50 treatments, after which blood is drawn every 8 to 12 weeks to prevent a re-build up of iron. A test that measures ferritin a protein involved in storing iron is commonly used to guide phlebotomy therapy in hemochromatosis patients. This study will compare the usefulness of the ferritin test with that of MCV, which measures red blood cell size, in guiding phlebotomy therapy. In addition, the study will 1) examine whether keeping iron levels low during maintenance therapy can help heal severe liver disease and improve arthritis in affected patients, and 2) design a system for making blood collected from hemochromatosis donors available for transfusion into other patients. Patients 15 years and older with diagnosed hemochromatosis or very high iron levels suggesting possible hemochromatosis may be eligible for this study. Candidates will have a history, physical evaluation, review of medical records and blood tests, and complete a symptoms questionnaire. Participants will have the following procedures: - Phlebotomy therapy every 1 to 2 weeks, depending on iron levels - Blood sample collection for blood cell counts and iron studies at every phlebotomy session - Blood sample collection (about 2 tablespoons) every 1 to 2 weeks after iron stores have been depleted - Phlebotomy every 8 to 12 weeks after iron stores are used up to prevent re-build up of excess iron With each blood donation that will be made available for transfusion to other patients, participants will answer the same health history screening questions and undergo the same blood tests given to all regular volunteer blood donors. These include screening for the HIV and hepatitis viruses and for syphilis. Patients who meet height and weight requirements may be asked to consider "double red cell" donations using apheresis. In this procedure, whole blood is collected through a needle placed in an arm vein, similar to routine phlebotomy. The blood then circulates through a machine that separates it into its components. The red cells are removed and the rest of the blood is returned to the body, either through the same needle or through a second needle in the other arm. Patients who have very high iron levels or an enlarged liver will be offered evaluation by the NIH Liver Service. Those judged to be at increased risk for cirrhosis may be advised to undergo a liver biopsy. If cirrhosis is found, the patient will be asked to consider a repeat biopsy after 3 to 5 years of continuous iron depletion to see if scarring has improved. Patients with arthritis will be offered evaluation by the NIH Arthritis Service and, depending on symptoms, may be advised to have X-ray studies or a joint biopsy.

NCT00007150 Hemochromatosis Procedure: Phlebotomy
MeSH: Hemochromatosis

- INCLUSION CRITERIA: Confirmed diagnosis of HH, defined by the following HFE genotypes: C282Y/C282 or C282Y/H63D. --- C282Y ---

Although the molecular pathophysiology remains incompletely understood, a homozygous mutation in the HFE gene (Cys282Tyr) is observed in nearly 100% of clinically confirmed cases. --- Cys282Tyr ---

Primary Outcomes

Description: Response to phlebotomy therapy in HH patients, as evidenced by iron-depletion

Measure: MCV drops 1-3% below baseline

Time: 4 to 12 months after starting phlebotomy therapy

3 Treatment of Nonalcoholic Steatohepatitis With Pioglitazone

This study will evaluate the effectiveness of pioglitazone, a new diabetes medicine, on decreasing insulin resistance and improving liver disease in patients with nonalcoholic steatohepatitis (NASH). NASH is a chronic liver disease with unknown cause that involves fat accumulation and inflammation in the liver, leading to liver cirrhosis in 10 to 15 percent of patients and significant liver scarring in another 30 percent. Although similar to a condition that affects people who drink excessive amounts of alcohol, NASH occurs in people who drink only minimal or no alcohol. It is most often seen in patients with insulin resistance. Pioglitazone decreases insulin resistance and improves blood lipid (fat) levels, so that it may improve liver disease in NASH. Patients with NASH 18 years of age or older may be eligible for this study. Candidates will be screened with a medical history and physical examination and routine blood tests. They will see a dietitian for counseling on diet and weight reduction, if needed. They will stop taking any medications for liver disease and take a daily multivitamin pill. After 2 months, those eligible for participation will be enrolled in the study. Participants will be admitted to the Clinical Center for 2 to 3 days for a complete medical history, physical examination, blood tests, urinalysis, chest X-ray, electrocardiogram, abdominal ultrasound and a liver biopsy. After the diagnosis of NASH is confirmed, the following procedures will be performed: - Echocardiography - imaging test using sound waves shows the heart structure and function - Resting metabolic rate - measures amount of oxygen (and calories) used to maintain body functions at rest. While lying down, the patient wears a clear plastic hood over the head for 20 minutes while the amount of oxygen used is measured. - Magnetic resonance imaging (MRI) scans - shows the size of the liver and other organs. The patient lies on a table in a metal cylinder that contains a magnetic field (the scanner) for no more than 30 minutes while the organs are imaged. - Dual energy X-ray absorptiometry (DEXA) scan measures whole body composition, including amount of fat. The patient lies under an X-ray scanning machine for about 2 minutes. - Oral glucose tolerance test (OGTT) - measures blood sugar and insulin levels. The patient drinks a very sweet drink containing glucose (sugar), after which blood samples are collected at various intervals during the 3-hour test. The blood is drawn through a catheter (thin plastic tube) placed in the arm before the test begins. - Intravenous glucose tolerance test (IVGTT) - determines how the tissues respond to insulin and glucose. Glucose is injected into a vein, followed by a short infusion of insulin. Blood samples are collected through a catheter at various intervals during the 3-hour test. When the above procedures are completed, patients start taking pioglitazone by mouth once a day for 48 weeks, keeping track of the medication and any side effects. They will be seen at the clinic every 2 weeks for the first month and then every 4 weeks for the rest of the treatment period. The visits will include an interview and examination by a physician and blood draw for laboratory tests. Female patients will have a pregnancy test at each clinic visit. At the end of the treatment period patients will be admitted to the Clinical Center for a repeat medical evaluation that will include the procedures described above.

NCT00013598 Fatty Liver Nonalcoholic Steatohepatitis Drug: Pioglitazone
MeSH: Fatty Liver Non-alcoholic Fatty Liver Disease
HPO: Hepatic steatosis

Hemochromatosis as defined by presence of 3+ or 4+ stainable iron on liver biopsy and homozygosity for C282Y or compound heterozygosity for C282Y/H63D. --- C282Y ---


4 Long-Term Treatment of Nonalcoholic Steatohepatitis With Pioglitazone

Nonalcoholic steatohepatitis (NASH) is a common liver disease that resembles alcoholic hepatitis but occurs in persons who drink little or no alcohol. The etiology of NASH is unclear, but it is commonly associated with diabetes, obesity, and insulin resistance. Several pilot studies, including a study of pioglitazone at the NIH Clinical Center (01-DK-0130), have shown that the insulin-sensitizing thiazolidinediones lead to decreases in serum alanine aminotransferase (ALT) levels and improved liver histology. Once therapy is stopped, however, ALT levels rapidly return to pre-treatment values. Inaddition we are currently enrolling patients with NASH in a pilot study of metformin therapy for 48-weeks, however our results in 3 patients thus far have not been very encouraging. In the current study, patients who have completed the pilot study of pioglitazone and have been off therapy for 48 weeks will be offered re-treatment for 3 years. We also propose to treat patients who have not had a satisfactory response to metformin with pioglitazone for the same duration. After a repeat medical and metabolic evaluation and liver biopsy, patients with moderate-to-severe NASH (activity score greater than or equal to 4) will restart pioglitazone at a dose of 15 mg daily. If after 48 weeks, ALT levels are not normal or improved to the degree identified during the pilot study, the dose will be increased to 30 mg daily at the end of 3 years, all patients will undergo repeat medical and metabolic evaluation and liver biopsy. The primary end point will be improvement in liver histology. Secondary end points will be improvements in insulin sensitivity, reduction in visceral fat, liver volume, and liver biochemistry. The aim of this study is to evaluate whether long-term pioglitazone therapy can safely achieve and maintain biochemical and histological improvements in NASH. ...

NCT00062764 Hepatitis Drug: Actos (Pioglitazone)
MeSH: Hepatitis Fatty Liver Non-alcoholic Fatty Liver Disease
HPO: Hepatic steatosis Hepatitis

Hemochromatosis as defined by presence of 3+ or 4 iron on liver biopsy stain and homozygosity for C282Y or compound heterozygosity for C282Y/H63D. --- C282Y ---

Primary Outcomes

Description: A histological response was defined as a reduction in the NASH activity index by 3 points or more with improvements of at least 1 point each in steatosis, parenchymal inflammation, and hepatocellular injury.

Measure: Number of Patients With Improvement in Liver Histology

Time: 48 weeks

Secondary Outcomes

Measure: Number of Patients With Impaired Glucose Tolerance After Treatment

Time: 48 weeks

Measure: Mean Increase of Insulin Sensitivity Index

Time: 48 weeks

Measure: Average Increase in Weight After Treatment

Time: 48 weeks

Measure: Mean BMI Change

Time: 48 weeks

5 Treatment of Nonalcoholic Steatohepatitis With Metformin

Nonalcoholic Steatohepatitis (NASH) is associated with progressive liver disease, fibrosis, and cirrhosis. Although the cause of NASH is unknown, it is often associated with obesity, type 2 diabetes, and insulin resistance. At present, there are no approved treatments for NASH patients, but an experimental approach has focused on improving their insulin sensitivity. Metformin is one of the most commonly used medications for the treatment of diabetes. The purpose of this study is to determine whether the medical problems of NASH patients, specifically liver damage, improves when their insulin sensitivity is enhanced with metformin. The study will last 3 to 5 years and will enroll up to 30 patients. Participants will undergo a complete medical examination, a series of lab tests, and a liver biopsy. They will then start taking a single 500-mg tablet of metformin once a day for 2 weeks, then the same dosage twice a day for 2 more weeks, if they tolerate the first dosage. The dosage will increase to 1,000 mg twice a day for the remaining 44 weeks of the study. After 1 year, participants will undergo a repeat medical examination and liver biopsy.

NCT00063232 Hepatitis Drug: Metformin
MeSH: Hepatitis Fatty Liver Non-alcoholic Fatty Liver Disease
HPO: Hepatic steatosis Hepatitis

7. Hemochromatosis as defined by presence of 3+ or 4+ stainable iron on liver biopsy and homozygosity for C282Y or compound heterozygosity for C282Y/H63D. --- C282Y ---

Primary Outcomes

Description: Patients under went liver biopsy, metabolic profiling and imaging studies before and at the end 48 weeks of metformin (2000 mg/day) therapy. The primary endpoint is a three point improvement in the histological NASH activity index with a decrease in at least two of the component scores and no worsening of fibrosis or increase in Mallory bodies.

Measure: Change in the Histological NASH Activity Index at 48 Weeks Compared With Baseline (Number of Participants in Each Change Category)

Time: from baseline to 48 Weeks

Secondary Outcomes

Description: Alanine transaminase <42 U/L is considered normal

Measure: Change in Serum Alanine Aminotransferase (ALT) Levels From Baseline (Number of Participants in Each Change Category)

Time: from baseline to 48 weeks

Description: HOMA-IR is calculated from Fasting Glucose and Fasting Insulin

Measure: Change in Insulin Sensitivity (Glucose Tolerance, Homeostatic Model Assessment of Insulin Resistence (HOMA-IR)) From Baseline

Time: from baseline to 48 weeks

6 Characterization of Cardiac Function in Subjects With Hereditary Hemochromatosis Who Are New York Heart Association Functional Class I

This study will examine the effect of iron buildup in the hearts of patients with hereditary hemochromatosis (HH), a genetic disease that causes the body to accumulate excess amounts of iron. The excess iron can damage the heart, liver, pancreas, skin, and joints. Generally, early treatment with phlebotomy (periodic removal of a unit of blood), and in some cases chelation (using a drug to remove iron from the body) slows down organ damage in HH patients. This study will try to elucidate the effect of iron buildup in the heart and determine if phlebotomy and chelation help keep the heart healthy. Patients with HH and healthy volunteers 21 years of age and older may be eligible for this study. (Normal volunteers will provide normal values of heart function that will be used to verify abnormalities detected in HH patients.) Patients must have a gene abnormality of Hfe gene Cys282Try homozygote. They may or may not be receiving treatment for HH and they must have no heart symptoms or serious organ damage due to HH. Candidates will be screened with a medical history and physical examination, blood tests, electrocardiogram (EKG), Holter EKG (24-hour EKG monitoring, see description below), and chest x-ray. Participants will undergo the following tests and procedures over 2 to 5 days: - Exercise test: The participant exercises on a treadmill while wearing a mouthpiece, which is used to measure how much oxygen is used. Electrodes placed on the chest and arms monitor the heartbeat during the test. - Echocardiography: This ultrasound test uses sound waves to take pictures. A small probe is held against the chest to allow a technician to take pictures of the heart and assess its function. A drug called Optison may be injected in an arm vein if needed to enhance the ultrasound images. - Exercise stress echocardiography: The participant exercises on a stationary bike while heart function is measured with an echocardiogram, EKG, and blood pressure cuff. - 24-hour Holter EKG: The participant wears a small machine that records heart rhythm continuously for 24 hours. The recorder is connected by cables to electrodes placed on the chest. - Magnetic resonance imaging: This test uses a magnetic field and radio waves to obtain detailed images of the heart and blood vessels. The participant lies flat on a table that slides inside the scanner, which is a large hollow tube. All tests are performed once in normal volunteers and in patients who have received standard treatment for HH. Untreated patients repeat the tests 6 months after beginning phlebotomy or chelation. Additional time points for these tests might be added if further evaluation is needed.

NCT00068159 Hereditary Hemochromatosis
MeSH: Hemochromatosis

- INCLUSION CRITERIA: HH Patients Group A patients (untreated HH patients) Adults 21 years or older New York Heart Association Functional Classification Class I Documented positive phenotyping for homozygote Cys282Tyr of Hfe gene with documented serum ferritin level above 400 ng/ml or documented % iron saturation more than 60%. --- Cys282Tyr ---

Group B patients (treated HH patients) Adults 21 years or older New York Heart Association Functional Classification Class I Documented positive phenotyping for homozygote Cys282Tyr of Hfe gene with documented serum ferritin level above 400 ng/ml or documented % iron saturation more than 60%. --- Cys282Tyr ---

No symptoms suggestive of heart disease or any other medical conditions, negative Hfe genotyping for Cys282Tyr or His63Asp with normal ferritin and iron saturation. --- Cys282Tyr ---

Homozygosity for the Cys282Tyr mutation, which is the most common known mutation with a predisposition to iron overload, occurs with an estimated frequency of 8 per 1000 in the Caucasians. --- Cys282Tyr ---

Although the pathophysiology remains incompletely understood, a homozygote mutation in Cys282Tyr is present in 84 to 100% of clinically confirmed HH cases. --- Cys282Tyr ---

Primary Outcomes

Description: To assess detailed cardiac function using non-invasive cardiac imaging in Group A; untreated-NYHA Class I HH subjects without conventional therapy for HH, Group B; treated- NYHA Class I HH subjects with conventional phlebotomy and/or iron chelation therapy and compare these results to those from Group C; age-gender matched healthy control volunteers.

Measure: Echocardographic variable early diastolic peak tissue Doppler velocity of septal mitral annulus (Em).

Time: Baseline, 1, 2, and 5 years

Secondary Outcomes

Description: To compare the results of the cardiac functional abnormalities in HH to those from healthy control volunteers

Measure: Exercise testing variable change in ejection fraction in response to exercise

Time: Baseline only

7 A Randomized Controlled Trial to Evaluate the Safety and Efficacy of Twice-Weekly Peginterferon Alpha 2a and Ribavirin Induction Therapy for Chronic Hepatitis C in Patients Who Are Coinfected With HIV-1

This study will evaluate the safety and effectiveness of combination therapy with peginterferon alpha-2a and ribavirin for treating hepatitis C virus (HCV) infection in HIV-infected patients. Peginterferon alpha with ribavirin is the therapy of choice for people with HCV alone. Peginterferon alpha-2a is a compound that results from attaching a polyethylene glycol molecule to interferon alpha-2a. This compound stays in the blood longer than unmodified interferon alpha-2a, causing a higher blood concentration and thus maintaining greater activity against the hepatitis C virus. HIV-infected patients 18 years of age and older with chronic hepatitis C infection and a viral load greater than 2000 copies/mL may be eligible for this 2-1/2 year study. Candidates are screened with a medical history and physical examination, blood and urine tests, eye examination, chest x-ray, electrocardiogram (EKG), liver ultrasound, and pregnancy test in women who are able to become pregnant. If a recent liver biopsy is not available, this test is done to determine the type and severity of liver disease. The patient is given a sedative before the procedure. Then, the skin in the area over the biopsy site is numbed with a local anesthetic and a needle is inserted rapidly into and out of the liver to obtain a small tissue sample. The patient remains in the hospital overnight for monitoring. Participants begin treatment with injections under the skin of peginterferon alpha-2a and ribavirin pills by mouth on study day 0. Peginterferon is given either once or twice a week for 4 weeks and then once a week for 44 weeks. Ribavirin is given daily. In addition, patients continue to take all other medications prescribed by their doctor. Clinic visits are scheduled for the following procedures: - Days 1, 3, 4, 7, 10 and weeks 2, 3, and 4 - Blood tests for safety measures and to measure blood levels of HIV and HCV. - Weeks 6, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44 - Blood and urine tests to determine the side effects of treatment and its effect on the HCV infection. In addition, eye examinations are done every 3 months, and pregnancy and thyroid function tests are done several times during the treatment period. - Week 48 or end of treatment - Treatment stops after 48 weeks. At this time, or earlier for those who do not complete the 48 weeks, patients return to the clinic for a chest x-ray, EKG, blood tests, and abdominal ultrasound. Patients are hospitalized for a repeat liver biopsy. - Weeks 52, 56, 64 and 72 - Blood and urine tests to determine the side effects of treatment and its effect on the HCV infection, and a urine pregnancy test in women.

NCT00085917 Hepatitis C HIV Infections Drug: Double dose pegylated interferon with weight based Ribavirin Drug: standard dose pegylated interferon alfa -2a and ribavirin
MeSH: Hepatitis A Hepatitis C Hepatitis
HPO: Hepatitis

- Hemochromatosis or secondary iron overload as defined by (1) an elevated serum ferritin or an iron saturation (serum iron/IBC X 100%) of greater than 50% and (2) presence of 3+ or more stainable Iron on liver biopsy according to the study pathologist or a history of previous phlebotomy for Iron overload will undergo HFE genetic counseling and those with a positive HFE genetic test demonstrating homozygosity for C282Y and H63D are not eligible. --- C282Y ---

Those who have compound heterozygosity to C282Y and H63D are also not eligible. --- C282Y ---

Primary Outcomes

Description: SVR [ Sustained virological response] SVR was defined as HCV RNA levels below the limit of detection 24 weeks after the end of treatment.

Measure: Number of Participants With Sustained Virologic Response (SVR)

Time: 72 weeks

Secondary Outcomes

Description: normalization of liver enzymes :Alanine aminotransferase (ALT) and Aspartate aminotransferase (AST) Alanine aminotransferase (ALT): Normal 6 - 41 U/L Aspartate aminotransferase (AST) : Normal 9 - 34 U/L

Measure: Number of Participants With Normalization of Liver Enzymes

Time: week 24, week 48, week 72

Description: Adverse Events - Anemia, Neutropenia and Psychiatric adverse events

Measure: Number of Participants With Adverse Events

Time: 48 weeks

8 S-Adenosyl Methionine for Symptomatic Treatment of Primary Biliary Cirrhosis

This study will examine the effect of S-adenosyl methionine (SAMe) on itching and fatigue in patients with primary biliary cirrhosis, a disease of the small bile ducts in the liver. Ursodiol, the only currently available treatment for biliary cirrhosis, does not cure the disease, and many people continue to have symptoms or liver test abnormalities despite treatment. SAMe is a naturally occurring substance found in most cells of the body. The highest levels of the substance are produced by the liver, where it helps to rid the body of toxins and breakdown products of metabolism. Studies in Europe suggest that SAMe may help to: 1) decrease the fatigue and itching that are common in persons with liver problems, and 2) decrease levels of liver enzymes in the blood, suggesting that it may decrease the amount of liver injury. Patients 21 years of age or older with primary biliary cirrhosis who are taking ursodiol and have symptoms of itching or fatigue may be eligible for this study. Candidates are screened with a medical history, physical examination, review of medical records, routine blood tests, and a symptoms rating scale. Participants stop all medications for itching 4 weeks before starting the study, but continue to take ursodiol during the 42-week trial. On entering the study, patients are assigned to take either SAMe or placebo tablets twice a day for 12 weeks. While taking the medications, they are followed in the clinic every 2 weeks for the first month and then every 4 weeks to fill out symptoms questionnaires and have a short medical evaluation and blood tests. At the end of 12 weeks, treatment is interrupted for a 2-week "wash-out" period, after which patients begin a 12-week crossover treatment; that is, patients who were taking SAMe are switched to placebo, and those who were taking placebo are switched to SAMe. After completing the second 12-week treatment course, patients come to the clinic at 4, 8, and 12 weeks to fill out symptoms questionnaires and have a medical evaluation and blood tests. At the last visit, patients are told which type of tablet they received during the two courses of treatment. SAMe is available without prescription in many forms as an over-the-counter medication.

NCT00125281 Liver Cirrhosis, Biliary Drug: S-adenosyl-methionine (SAMe) capsules
MeSH: Liver Cirrhosis Liver Cirrhosis, Biliary Fibrosis
HPO: Biliary cirrhosis Cirrhosis Hepatic fibrosis

Hemochromatosis as defined by presence of 3+ or 4+ stainable iron on liver biopsy and homozygosity for C282Y or compound heterozygosity for C282Y/H63D. --- C282Y ---

Patients with iron saturation indices of greater than 45% and serum ferritin levels of greater than 300 ng/ml for men and greater than or equal to 250 ng/ml for women will undergo genetic testing for C282Y and H63D. --- C282Y ---

Primary Outcomes

Measure: Improvement in symptoms as assessed by validated questionnaires and visual analogue scales administered at 2 to 4 week intervals during therapy.

Time: 12 weeks of therapy

Secondary Outcomes

Measure: Improvement in serum alanine aminotransferase and alkaline phosphatase.

Time: 12 weeks

9 Cytochrome P450 2E1 and Iron Overload

The aim of the study is to determine, in patients presenting hepatic iron overload (genetic haemochtomatisis or dysmetabolic iron overload syndrome), the effects of venesection therapy on cytochrome P450 2E1 activity by comparing the rates of metabolization of chlorzoxazone before and after venesection.

NCT00138684 Insulin Resistance Iron Overload Procedure: venesection
MeSH: Insulin Resistance Iron Overload
HPO: Insulin resistance

Inclusion Criteria: - Male patients aged from 18 to 70 years - Hepatic iron overload measured by magnetic resonance imaging [MRI] (> 36 µmol/g and < 200 µmol/L) - Homozygosity for the C282Y mutation of the HFE or dysmetabolic iron overload syndrome (DIOS) based on the presence of at least one of these following metabolic abnormalities: - Overweight: BMI > 25 kg/m2 - Waist/hip circumference (cm) > 0.90 - Diabetes mellitus (fasting blood glucose level >1.25g/L or blood glucose level after 2 hours > 2g/L) or glucose intolerance (fasting blood glucose level between 1.10 and 1.25g/L) - Total cholesterolemia > 6.2 mmol/L or HDL-Cholesterol < 0.9 mmol/L - TG>= 1.7 mmol - Written informed consent Non-Inclusion Criteria: - Consumption of alcohol > 50 g/day and of any CYP2E1 inhibitor substances - Smoker > 5 cigarets/day - History of blood donation or venesection - Other causes of iron overload: aceruloplasminaemia, haematological disorder (abnormal blood counting), late cutaneous porphyria (cutaneous bullous disorders and photosensibilisation) , martial treatment, repeated transfusions. --- C282Y ---

- Inflammatory syndrome (CRP > 3ng/ml) Inclusion Criteria: - Male patients aged from 18 to 70 years - Hepatic iron overload measured by magnetic resonance imaging [MRI] (> 36 µmol/g and < 200 µmol/L) - Homozygosity for the C282Y mutation of the HFE or dysmetabolic iron overload syndrome (DIOS) based on the presence of at least one of these following metabolic abnormalities: - Overweight: BMI > 25 kg/m2 - Waist/hip circumference (cm) > 0.90 - Diabetes mellitus (fasting blood glucose level >1.25g/L or blood glucose level after 2 hours > 2g/L) or glucose intolerance (fasting blood glucose level between 1.10 and 1.25g/L) - Total cholesterolemia > 6.2 mmol/L or HDL-Cholesterol < 0.9 mmol/L - TG>= 1.7 mmol - Written informed consent Non-Inclusion Criteria: - Consumption of alcohol > 50 g/day and of any CYP2E1 inhibitor substances - Smoker > 5 cigarets/day - History of blood donation or venesection - Other causes of iron overload: aceruloplasminaemia, haematological disorder (abnormal blood counting), late cutaneous porphyria (cutaneous bullous disorders and photosensibilisation) , martial treatment, repeated transfusions. --- C282Y ---

Primary Outcomes

Measure: variation of chlorzoxazone metabolization rate measured before and after venesection

Time: Baseline and after iron desaturation completion

Secondary Outcomes

Measure: variation of blood Malonedialdehyde rate

Time: Baseline and after iron desaturation completion

Measure: variation of blood 4-hydroxynonenal rate

Time: Baseline and after iron desaturation completion

Measure: variation of blood Glutathion rate

Time: Baseline and after iron desaturation completion

Measure: variation of serum Vitamin E rate

Time: Baseline and after iron desaturation completion

Measure: Variation of serum Vitamin C rate

Time: Baseline and after iron desaturation completion

10 Iron Depletion Therapy for Patients With Type 2 Diabetes Mellitus and Non-Alcoholic Fatty Liver Disease

The purpose of this study is to find out whether lowering the amount of iron in the body will result in less resistance to insulin and improved liver function in patients with type 2 diabetes mellitus and non-alcoholic fatty liver disease. This may result in better diabetes control and/or a decrease in the amount of liver fat.

NCT00230087 Non-Alcoholic Fatty Liver Disease Diabetes Mellitus Procedure: blood donation
MeSH: Liver Diseases Fatty Liver Non-alcoholic Fatty Liver Disease Diabetes Mellitus
HPO: Abnormality of the liver Decreased liver function Diabetes mellitus Elevated hepatic transaminase Hepatic steatosis

- Hemoglobin HbA1c level ≤ 8 % - Serum ALT levels ≥1.3 x ULN - Between 18-65 years of age Exclusion Criteria - Hereditary hemochromatosis or hepatic iron overload defined as any of the following: - 2+ iron on hepatic iron staining - Hepatic Iron Index ≥ 1.9 - C282Y homozygous or C282Y/H63D compound heterozygous HFE genotype - Use of insulin or thiazolidinediones for the treatment of diabetes - Use of anti-NASH drugs (thiazolidinediones, vitamin E, UDCA, SAM-e, betaine, milk thistle, gemfibrozil, anti-TNF therapies, probiotics) - Serum ferritin <50μg/L - Serum transferrin-iron saturation <10 % - Hemoglobin <10 mg/L - Hematocrit <38 % - Voluntary blood donation or therapeutic phlebotomy within the previous twelve months (except routine lab tests) - Pregnant or lactating women - Prior history of coronary artery disease, myocardial infarction, exertional dyspnea or chronic chest pain at rest. - Evidence of myocardial infarction as determined by an ECG Inclusion Criteria - Histological evidence of NAFLD and enrollment in NASH CRN Database Study - Type 2 DM treated with diet or a stable dose of non-insulin sensitizing oral hypoglycemic agents for > 3 mo. --- C282Y ---

- Hemoglobin HbA1c level ≤ 8 % - Serum ALT levels ≥1.3 x ULN - Between 18-65 years of age Exclusion Criteria - Hereditary hemochromatosis or hepatic iron overload defined as any of the following: - 2+ iron on hepatic iron staining - Hepatic Iron Index ≥ 1.9 - C282Y homozygous or C282Y/H63D compound heterozygous HFE genotype - Use of insulin or thiazolidinediones for the treatment of diabetes - Use of anti-NASH drugs (thiazolidinediones, vitamin E, UDCA, SAM-e, betaine, milk thistle, gemfibrozil, anti-TNF therapies, probiotics) - Serum ferritin <50μg/L - Serum transferrin-iron saturation <10 % - Hemoglobin <10 mg/L - Hematocrit <38 % - Voluntary blood donation or therapeutic phlebotomy within the previous twelve months (except routine lab tests) - Pregnant or lactating women - Prior history of coronary artery disease, myocardial infarction, exertional dyspnea or chronic chest pain at rest. - Evidence of myocardial infarction as determined by an ECG Non-Alcoholic Fatty Liver Disease Diabetes Mellitus Liver Diseases Fatty Liver Non-alcoholic Fatty Liver Disease Diabetes Mellitus Nonalcoholic fatty liver disease (NAFLD) is a common liver disease in the United States. --- C282Y ---

Primary Outcomes

Measure: Improved insulin sensitivity as determined by:(1) hyperinsulinemic euglycemic clamp method

Time: one year

Measure: (2) HOMA model- determined by the OGTT method

Time: one year

Secondary Outcomes

Measure: Change in serum aminotransferase levels Change in levels of serum, plasma and urinary markers of oxidative stress

Time: one year

Measure: Changes in intrahepatic and intraabdominal fat content as determined by CT scan

Time: one year

Measure: Change in serum levels of proinflammatory cytokines (ie IL-6, TnF-αR2)

Time: one year

11 Study of the Effects of Muscular Activity on Iron Metabolism: A Pilot Study on Healthy Volunteers

The aim of this study is to evaluate the effect of muscular exercise on iron metabolism in healthy volunteers. Fourteen healthy male subjects will have to pedal on an ergocycle for 45 minutes, and urine and blood samples will be collected regularly to measure hemojuvelin, hepcidin, iron and transferrin levels.

NCT00378469 Iron Overload Iron Deficiency Behavioral: 45 minute exercise on ergocycle
MeSH: Iron Overload

Inclusion Criteria: - Male individuals aged between 18 and 40 years old - Body mass index (BMI) between 18 and 25 - Normal at clinical examination - Normal biological variables - Written informed consent Exclusion Criteria: - Mutation C282Y of the HFE gene - Iron metabolism abnormality - Inflammatory syndrome - Chronic pathology or ongoing treatment - Tobacco smoking, alcohol consuming more than 30g/day - History of transfusion or blood-giving within 3 months - Positive serology for hepatitis B virus (HBV), hepatitis C virus (HCV) or HIV. --- C282Y ---

Primary Outcomes

Measure: Pharmacokinetics of urinary hepcidin

Measure: Pharmacokinetics of blood hemojuvelin

Secondary Outcomes

Measure: Pharmacokinetics of urine and blood iron, transferrin, interleukin-6 (IL-6) and ferritin

12 A Phase I/II Open Label, Dose Escalation Trial and a Six Month Extension to Explore the Safety and Efficacy of ICL670 in Patients With Iron Overload Resulting From Hereditary Hemochromatosis.

Brief Summary: This study was designed to explore a safe dose and characterize the preliminary safety and efficacy of ICL670 in adult patients with previously documented history of homozygous C282Y.

NCT00395629 Iron Overload Hereditary Hemochromatosis Drug: Deferasirox (ICL670)
MeSH: Hemochromatosis Iron Overload

A Phase I/II Open Label, Dose Escalation Trial and a Six Month Extension to Explore the Safety and Efficacy of ICL670 in Patients With Iron Overload Resulting From Hereditary Hemochromatosis.. Safety and Efficacy of Deferasirox (ICL670) in Patients With Iron Overload Resulting From Hereditary Hemochromatosis Brief Summary: This study was designed to explore a safe dose and characterize the preliminary safety and efficacy of ICL670 in adult patients with previously documented history of homozygous C282Y. --- C282Y ---

The mean trough concentration at each time point was calculated.. Inclusion Criteria: - Age 18 years of age or older - Male or female patients homozygous for the C282Y mutation. --- C282Y ---

Inclusion Criteria: - Age 18 years of age or older - Male or female patients homozygous for the C282Y mutation. --- C282Y ---

Primary Outcomes

Description: Mean absolute change in serum ferritin from baseline to the end of the extension study.

Measure: Absolute Change of Serum Ferritin From Baseline to the End of Extension, by Dose Cohort (Extension Per-protocol Population)

Time: 0 to 48 weeks

Secondary Outcomes

Description: A blood sample was collected just prior to administration of the next dose of Deferasirox (pre-dose trough level) or approximately 24 hours after the previous dose at weeks 4, 8, 12, 16, 20 and 24. The mean trough concentration at each time point was calculated.

Measure: Trough Concentrations of Deferasirox (ICL670), by Dose Cohort (Per-protocol Population)

Time: 4, 8, 12, 16, 20, and 24 weeks

13 Efficacy and Safety of Ursodesoxycholic Acid in the Management of Non-Alcoholic Steatohepatitis

This is a phase II study with direct individual benefit. It is a randomized, double blind placebo controlled study whose aim is to evaluate the efficacy and tolerance of ursodesoxycholic acid in patients who have been diagnosed with non-alcoholic steatohepatitis. The hepatoprotective effects of ursodesoxycholic acid may ameliorate the hepatic impairment associated with non-alcoholic steatohepatitis leading to subsequent significant decreases in transaminase elevations and non-invasive markers for hepatic fibrosis A positive response is defined as a significantly larger decrease in average ALAT levels between the time of inclusion in the study and the end of the treatment for the ursodesoxycholic acid group as compared to the placebo group. The duration of the study will be 12 months. An end of treatment evaluation (EoT) will take place at the end of the 12th month of treatment.

NCT00470171 Serum Levels of ALAT Transaminases Serum Markers for Fibrosis and Hepatic Inflammation Drug: Ursodesoxycholic acid
MeSH: Fatty Liver Non-alcoholic Fatty Liver Disease Inflammation
HPO: Hepatic steatosis

- Alcohol consumption of >20 g/day for women and > 30 g/day for men - Hepatitis from other causes: chronic viral hepatitis B or C, elevated ferritin levels associated with C282Y homozygosity, primary biliary cirrhosis, primary sclerosing cholangitis, well documented auto-immune hepatitis (specific autoantibodies, hypergammaglobulinemia, consistent histologic changes), alpha1 antitrypsin deficiency, Wilson's disease, HIV infection. --- C282Y ---

Primary Outcomes

Measure: A positive response is defined as a significantly larger decrease in average ALAT levels between the time of inclusion in the study and the end of the treatment for the ursodesoxycholic acid group as compared to the placebo group.

14 Effects of S-Adenosyl Methionine (SAMe) on Viral and Cell Signaling Response to Combination Therapy for Chronic Hepatitis C

This study will examine the effectiveness of S-adenosyl methionine (SAMe) in combination with peginterferon and ribavirin for treating hepatitis C virus. One out of three patients with hepatitis C develops cirrhosis of the liver, which can lead to liver failure or liver cancer. SAMe is a nutritional supplement that is made naturally in all cells of the body and acts to improve how the body handles stress. In laboratory experiments with liver cells, SAMe decreases the injury caused by liver toxins and improves the ability of interferon to block hepatitis C virus. Patients 18 years of age and older with hepatitis C infection who did not respond successfully to prior treatment with interferon and ribavirin or peginterferon and ribavirin may be eligible for this study. Participants receive the following treatment: - Peginterferon (given by injection) and ribavirin (taken by mouth) for 2 weeks - Washout period (no medications) for 4 weeks - SAMe (taken by mouth) for 2 weeks - Peginterferon, ribavirin and SAMe for 12-48 weeks, depending on patient response to treatment. Participants have a thorough physical evaluation before beginning treatment and again at the study's end. After starting treatment, patients return for clinic visits and blood tests weekly for the first several weeks, then less frequently (at 2-week, then 4-week and 8-week intervals until up to 72 weeks) to monitor symptoms, drug side effects, hepatitis C virus levels, liver enzyme levels and immune responses to hepatitis C. ...

NCT00475176 Chronic Hepatitis C Drug: Peginterferon alfa-2a Drug: Ribavirin Drug: S-adenosyl methionine for Chronic Liver Disease
MeSH: Hepatitis A Hepatitis C Hepatitis C, Chronic Hepatitis Hepatitis, Chronic
HPO: Chronic active hepatitis Chronic hepatitis Hepatitis

- Hemochromatosis as defined by presence of 3+ or 4+ stainable iron on liver biopsy and homozygosity for C282Y or compound heterozygosity for C282Y/H63D. --- C282Y ---

Patients with iron saturation indices of greater than 45% and serum ferritin levels of greater than 300 ng/ml for men and greater than 250 ng/ml for women will undergo genetic testing for C282Y and H63D. --- C282Y ---

Primary Outcomes

Description: Improvement of slopes of decline in hepatitis C virus Ribonucleic acid in second course compared with first course in days 7 to 14 of therapy

Measure: Improvement in Viral Kinetics During the First 2 Weeks of Therapy

Time: Days 7 to 14 of therapy

Secondary Outcomes

Description: 2-log decline in HCV RNA by week 12 (early virological response) and sustained eradication of HCV RNA (sustained virological response).

Measure: 2-log Decline in HCV RNA by Week 12 (Early Virological Response) and Sustained Eradication of HCV RNA (Sustained Virological Response).

Time: 12 weeks from start of therapy

15 An Open Label Non-Randomized Trial to Assess Safety and Tolerability of Alb-Interferon Alfa 2b Every Two Weeks With Ribavirin Among HIV/HCV Coinfected Individuals

This study will determine if Albumin-linked interferon (Albinterferon alfa-2b) every 2 weeks is safe and tolerated by patients infected by both hepatitis C virus (HCV) and human immunodeficiency virus (HIV). This is a new medication developed for HCV. It may help the immune system fight infections, especially those caused by viruses. Albinterferon alfa-2b appears quite similar to other interferons, in side effects and action in controlling HCV. Patients ages 18 and older who are infected with HCV genotype 1, are HIV positive, are infected with HCV, and have evidence of HCV-induced liver disease; and who are not pregnant or breast feeding may be eligible for this study. Many visits to NIH over a 76-week period are required. There will be collection of blood and urine, pregnancy test, and tests of HCV in the blood. A liver biopsy is required before start of the study if patients have not had one within 1 year. Another is done at the end of 72 weeks. An eye exam is done before start of the study and repeated later. An optional procedure called automated pheresis is done at the study beginning. Researchers can study patients' immunity to control HCV. Blood is drawn through a needle in an arm vein and spun in a machine to separate the desired blood component. Remaining blood is returned to the patient. Patients will receive Albinterferon alfa-2b at a dose of 900 mcg every 2 weeks for 48 weeks, by injection under the skin. Ribavirin is given at 1,000 mg or 1,200 mg by mouth twice daily, depending on a patient's weight. Side effects of Albinterferon alfa-2b are fatigue, headache, joint and muscle pain, and sleeplessness. The major side effect of ribavirin is anemia. Visits ranging from week 3 to 44 will determine the safety of Albinterferon alfa-2b and ribavirin and to see effects on reducing the HCV viral load. For weeks 48, 52, 56, 64, 72, and 76, patients will return for a clinic visit and blood tests. At week 72, an abdominal ultrasound and liver biopsy are done. Week 76 includes discussion of biopsy results.

NCT00489385 HIV Infections HCV Drug: Albinterferon Drug: Ribavirin Drug: Albuferon
MeSH: HIV Infections

Those subjects with, or a history of previous phlebotomy for iron overload will undergo HFE genetic counseling and those with a positive HFE genetic test demonstrating homozygosity for C282Y and H63D are not eligible. --- C282Y ---

Those who have compound heterozygosity to C282Y and H63D are also not eligible. --- C282Y ---

Primary Outcomes

Measure: Safety and tolerability of two doses of Albinterferon alpha 2b with ribavirin.

Secondary Outcomes

Measure: Histologic, virologic responses to Albinterferon alpha 2b and ribavirin

16 Therapeutic Effect of Erythrocyte Apheresis as Compared to Full Blood Phlebotomy in Patients With Hereditary Hemochromatosis

Primary hemochromatosis is the most frequent hereditary condition in Scandinavia. The condition may result in serious organ damage which can be prevented by therapy, but only few patients develop such organ damage. The optimal treatment, therefore, is still a matter of discussion Prevention of organ damage has traditionally been accomplished by drawing of full blood (phlebotomy), which has to be frequently repeated during the initial phase and then continued indefinitely as a maintenance treatment. The removed amount of iron may be increased two- or threefold for each procedure by using modern equipment for selective removal of red blood cells (red cell apheresis). Possible drawbacks of this technique may be higher costs, prolonged time for each therapeutic procedure, and certain requirements to the patients. The possible advantages are the reduced number of therapeutic procedures and less strain for the patient. No larger, randomized study has been published in order to determine which method should be preferred. This study is a controlled trial in which participating patients are asked to be randomized to red cell apheresis or traditional phlebotomy. Each group will be followed by means of well-defined assessments in order to explore possible advantages and disadvantages of each method in order to establish what type of treatment should be recommended.

NCT00509652 Hemochromatosis Procedure: Arm 1: Erythrocyte apheresis Procedure: Arm 2: Whole blood phlebotomy
MeSH: Hemochromatosis

Inclusion Criteria: 1. Diagnosis - Individuals who art homozygous for C282Y or H63D or "compound heterozygous" for these tow variants and have ferritin levels higher than 300 micrograms/L or transferrin saturation higher than 50%. --- C282Y ---

- Individuals heterozygous for C282Y or H63D if ferritin levels higher than 500 micrograms/L or transferrin saturation higher than 50%. --- C282Y ---

Exclusion Criteria: 1. Contra-indications to either treatment modality 2. Patients who are not able to co-operate 3. Lack of informed consent Inclusion Criteria: 1. Diagnosis - Individuals who art homozygous for C282Y or H63D or "compound heterozygous" for these tow variants and have ferritin levels higher than 300 micrograms/L or transferrin saturation higher than 50%. --- C282Y ---

However, the criteria for ferritin levels have been set at 300 micrograms/L for patients who are homozygous for the C282Y mutation, and also heterozygous individuals will be included if ferritin is higher than 500 micrograms/L. --- C282Y ---

Inclusion criteria 1. Diagnosis 1. Individuals who art homozygous for C282Y or H63D or "compound heterozygous" for these tow variants and have ferritin levels higher than 300 micrograms/L or transferrin saturation higher than 50%. --- C282Y ---

2. Individuals heterozygous for C282Y or H63D if ferritin levels higher than 500 micrograms/L or transferrin saturation higher than 50%. --- C282Y ---

Primary Outcomes

Measure: Decline in ferritin levels and transferrin saturation

Secondary Outcomes

Measure: Decline in hemoglobin levels

Measure: Patient discomfort during therapeutic procedure

Measure: Time consumption

Measure: Costs

17 Effect of Iron Depletion by Phlebotomy Plus Lifestyle Changes vs. Lifestyle Changes Alone on Liver Damage in Patients With Nonalcoholic Fatty Liver Disease With Increased Iron Stores

Patients will be randomized to lifestyle changes alone or lifestyle changes associated with iron depletion. Iron depletion will be achieved by removing 350 cc of blood every 10-15 days according to baseline hemoglobin values and venesection tolerance, until ferritin < 30 ng/ml and transferrin saturation < 25%. Weekly phlebotomies will be allowed for carriers of the C282Y HFE mutation. Smaller phlebotomies (250 cc) will be allowed for carriers of beta-thalassaemia trait. Maintenance phlebotomies (as much as required) will then be instituted to keep iron stores depleted (ferritin < 50 ng/ml and transferrin saturation < 25%, MCV <85 fl). Before starting treatment, patients will undergo ECG, and in the presence of hyperglycemia or hypertension also echocardiography (see exclusion criteria). Change in diabetes medication dosage or start of new therapy will be allowed for HbA1C values <6% or ≥ 7%. According to accepted criteria, previously untreated patients should be treated with metformin. If possible, newly diagnosed hypertension should be treated with Ace-inhibitors.

NCT00658164 Nonalcoholic Fatty Liver Disease Other: Iron depletion treatment
MeSH: Liver Diseases Fatty Liver Non-alcoholic Fatty Liver Disease
HPO: Abnormality of the liver Decreased liver function Elevated hepatic transaminase Hepatic steatosis

Weekly phlebotomies will be allowed for carriers of the C282Y HFE mutation. --- C282Y ---

*Hemochromatosis, as defined by homozygosity for the C282Y HFE mutation or compound heterozygosity for C282Y/H63D mutations or Hepatic Iron Index ≥ 1.9. --- C282Y ---

Primary Outcomes

Measure: To determine in a 24 month controlled study whether iron depletion by phlebotomy improves insulin sensitivity, and thereby reduces hepatic steatosis and inflammation in subjects with nonalcoholic steatohepatitis

Time: 24 months

Secondary Outcomes

Measure: To assess the effect of iron depletion on glucose tolerance status. Glucose tolerance will be determined by OGTT in subjects without type 2 diabetes (T2D), and by HbA1c levels and the change in dosage of pharmacological therapy in those with T2D.

Time: 24 months

18 A Phase III, Randomized Study of the Effects of Parenteral Iron, Oral Iron, or No Iron Supplementation on the Erythropoietic Response to Darbepoetin Alfa for Cancer Patients With Chemotherapy-Associated Anemia

RATIONALE: Darbepoetin alfa may cause the body to make more red blood cells. Red blood cells contain iron that is needed to carry oxygen to the tissues. It is not yet known whether giving darbepoetin alfa (DA) together with intravenous iron or oral iron is more effective than giving darbepoetin alfa together with a placebo in treating anemia caused by chemotherapy. PURPOSE: This randomized phase III trial is studying giving darbepoetin alfa together with iron to see how well it works compared with giving darbepoetin alfa together with a placebo in treating anemia caused by chemotherapy in patients with cancer.

NCT00661999 Anemia Leukemia Lymphoma Lymphoproliferative Disorder Multiple Myeloma and Plasma Cell Neoplasm Precancerous Condition Unspecified Adult Solid Tumor, Protocol Specific Biological: darbepoetin alfa Dietary Supplement: ferrous sulfate Drug: sodium ferric gluconate complex in sucrose Other: placebo
MeSH: Lymphoma Leukemia Multiple Myeloma Neoplasms, Plasma Cell Precancerous Conditions Anemia Lymphoproliferative Disorders
HPO: Anemia Leukemia Lymphoma Lymphoproliferative disorder Multiple myeloma

DISEASE CHARACTERISTICS: - Diagnosis of a non-myeloid cancer (other than non-melanomatous skin cancer) - Receiving or scheduled to receive chemotherapy (biological agents, such as small molecules/tyrosine kinase inhibitors and antibody-based therapies, are allowed) - Has chemotherapy-related anemia (hemoglobin < 11 g/dL) - No anemia known to be secondary to gastrointestinal bleeding or hemolysis - No anemia known to be secondary to vitamin B12 or folic acid deficiency + Vitamin B12 and folic acid deficiency must be ruled out if the mean corpuscular volume (MCV) is > 100 fL - No anemia secondary to chemotherapy-induced myelodysplastic syndromes - No primary hematologic disorder causing moderate to severe anemia (e.g., congenital dyserythropoietic anemia, homozygous hemoglobin S disease or compound heterozygous sickling states, or thalassemia major) - Carriers for these disease states are eligible - No first-degree relative with primary hemochromatosis (unless the patient has undergone HFE genotyping and was found to have at least one wild-type allele, while the proband in the family demonstrated to have either the common C282Y or H63D mutation) PATIENT CHARACTERISTICS: - ECOG performance status 0-2 - Ferritin > 20 mcg/L (i.e., not obviously iron deficient) - ALT or AST < 5 times upper limit of normal - Alert, mentally competent, and able to sign informed consent - Not pregnant or nursing - Negative pregnancy test - Fertile patients must use effective contraception during and for 3 months after completion of study treatment - Willing or able to be randomized and undergo study treatment - Willing or able to fill out quality-of-life forms - No uncontrolled hypertension (i.e., systolic blood pressure [BP] ≥ 180 mm Hg or diastolic BP ≥ 100 mm Hg) - No history of uncontrolled cardiac arrhythmias - No pulmonary embolism or deep venous thrombosis within the past year (unless the patient is on anticoagulation therapy and planning to continue it during study participation) - No known hypersensitivity to darbepoetin alfa, erythropoietin, mammalian cell-derived products, iron, or human albumin - No seizures within the past 3 months - No gastrointestinal conditions expected to cause significant impairment of oral iron, such as untreated celiac disease or amyloidosis involving the gut - Patients with celiac disease who are adhering to a gluten-free diet are eligible PRIOR CONCURRENT THERAPY: - See Disease Characteristics - More than 3 months since prior darbepoetin alfa, epoetin alfa, or any investigational forms of erythropoietin (e.g., gene-activated erythropoietin or novel erythropoiesis-stimulating protein) - More than 1 year since prior peripheral blood stem cell or bone marrow transplantation - More than 2 weeks since prior red blood cell transfusions - More than 14 days since prior major surgery - No prior gastrectomy or resection of > 100 cm of small intestine - Not planning to undergo stem cell or bone marrow transplantation within the next 6 months DISEASE CHARACTERISTICS: - Diagnosis of a non-myeloid cancer (other than non-melanomatous skin cancer) - Receiving or scheduled to receive chemotherapy (biological agents, such as small molecules/tyrosine kinase inhibitors and antibody-based therapies, are allowed) - Has chemotherapy-related anemia (hemoglobin < 11 g/dL) - No anemia known to be secondary to gastrointestinal bleeding or hemolysis - No anemia known to be secondary to vitamin B12 or folic acid deficiency + Vitamin B12 and folic acid deficiency must be ruled out if the mean corpuscular volume (MCV) is > 100 fL - No anemia secondary to chemotherapy-induced myelodysplastic syndromes - No primary hematologic disorder causing moderate to severe anemia (e.g., congenital dyserythropoietic anemia, homozygous hemoglobin S disease or compound heterozygous sickling states, or thalassemia major) - Carriers for these disease states are eligible - No first-degree relative with primary hemochromatosis (unless the patient has undergone HFE genotyping and was found to have at least one wild-type allele, while the proband in the family demonstrated to have either the common C282Y or H63D mutation) PATIENT CHARACTERISTICS: - ECOG performance status 0-2 - Ferritin > 20 mcg/L (i.e., not obviously iron deficient) - ALT or AST < 5 times upper limit of normal - Alert, mentally competent, and able to sign informed consent - Not pregnant or nursing - Negative pregnancy test - Fertile patients must use effective contraception during and for 3 months after completion of study treatment - Willing or able to be randomized and undergo study treatment - Willing or able to fill out quality-of-life forms - No uncontrolled hypertension (i.e., systolic blood pressure [BP] ≥ 180 mm Hg or diastolic BP ≥ 100 mm Hg) - No history of uncontrolled cardiac arrhythmias - No pulmonary embolism or deep venous thrombosis within the past year (unless the patient is on anticoagulation therapy and planning to continue it during study participation) - No known hypersensitivity to darbepoetin alfa, erythropoietin, mammalian cell-derived products, iron, or human albumin - No seizures within the past 3 months - No gastrointestinal conditions expected to cause significant impairment of oral iron, such as untreated celiac disease or amyloidosis involving the gut - Patients with celiac disease who are adhering to a gluten-free diet are eligible PRIOR CONCURRENT THERAPY: - See Disease Characteristics - More than 3 months since prior darbepoetin alfa, epoetin alfa, or any investigational forms of erythropoietin (e.g., gene-activated erythropoietin or novel erythropoiesis-stimulating protein) - More than 1 year since prior peripheral blood stem cell or bone marrow transplantation - More than 2 weeks since prior red blood cell transfusions - More than 14 days since prior major surgery - No prior gastrectomy or resection of > 100 cm of small intestine - Not planning to undergo stem cell or bone marrow transplantation within the next 6 months Anemia Leukemia Lymphoma Lymphoproliferative Disorder Multiple Myeloma and Plasma Cell Neoplasm Precancerous Condition Unspecified Adult Solid Tumor, Protocol Specific Lymphoma Leukemia Multiple Myeloma Neoplasms, Plasma Cell Precancerous Conditions Anemia Lymphoproliferative Disorders OBJECTIVES: Primary * To compare the effects of IV iron, oral iron, or placebo in combination with darbepoetin alfa on the hematopoietic response rate, defined as a hemoglobin increment of ≥ 2.0 g/dL from baseline or achievement of hemoglobin of ≥ 11 g/dL in the absence of red blood cell transfusions (RBC) in the preceding 28 days of the treatment period, in cancer patients with chemotherapy-associated anemia. --- C282Y ---

DISEASE CHARACTERISTICS: - Diagnosis of a non-myeloid cancer (other than non-melanomatous skin cancer) - Receiving or scheduled to receive chemotherapy (biological agents, such as small molecules/tyrosine kinase inhibitors and antibody-based therapies, are allowed) - Has chemotherapy-related anemia (hemoglobin < 11 g/dL) - No anemia known to be secondary to gastrointestinal bleeding or hemolysis - No anemia known to be secondary to vitamin B12 or folic acid deficiency + Vitamin B12 and folic acid deficiency must be ruled out if the mean corpuscular volume (MCV) is > 100 fL - No anemia secondary to chemotherapy-induced myelodysplastic syndromes - No primary hematologic disorder causing moderate to severe anemia (e.g., congenital dyserythropoietic anemia, homozygous hemoglobin S disease or compound heterozygous sickling states, or thalassemia major) - Carriers for these disease states are eligible - No first-degree relative with primary hemochromatosis (unless the patient has undergone HFE genotyping and was found to have at least one wild-type allele, while the proband in the family demonstrated to have either the common C282Y or H63D mutation) PATIENT CHARACTERISTICS: - ECOG performance status 0-2 - Ferritin > 20 mcg/L (i.e., not obviously iron deficient) - ALT or AST < 5 times upper limit of normal - Alert, mentally competent, and able to sign informed consent - Not pregnant or nursing - Negative pregnancy test - Fertile patients must use effective contraception during and for 3 months after completion of study treatment - Willing or able to be randomized and undergo study treatment - Willing or able to fill out quality-of-life forms - No uncontrolled hypertension (i.e., systolic blood pressure [BP] ≥ 180 mm Hg or diastolic BP ≥ 100 mm Hg) - No history of uncontrolled cardiac arrhythmias - No pulmonary embolism or deep venous thrombosis within the past year (unless the patient is on anticoagulation therapy and planning to continue it during study participation) - No known hypersensitivity to darbepoetin alfa, erythropoietin, mammalian cell-derived products, iron, or human albumin - No seizures within the past 3 months - No gastrointestinal conditions expected to cause significant impairment of oral iron, such as untreated celiac disease or amyloidosis involving the gut - Patients with celiac disease who are adhering to a gluten-free diet are eligible PRIOR CONCURRENT THERAPY: - See Disease Characteristics - More than 3 months since prior darbepoetin alfa, epoetin alfa, or any investigational forms of erythropoietin (e.g., gene-activated erythropoietin or novel erythropoiesis-stimulating protein) - More than 1 year since prior peripheral blood stem cell or bone marrow transplantation - More than 2 weeks since prior red blood cell transfusions - More than 14 days since prior major surgery - No prior gastrectomy or resection of > 100 cm of small intestine - Not planning to undergo stem cell or bone marrow transplantation within the next 6 months DISEASE CHARACTERISTICS: - Diagnosis of a non-myeloid cancer (other than non-melanomatous skin cancer) - Receiving or scheduled to receive chemotherapy (biological agents, such as small molecules/tyrosine kinase inhibitors and antibody-based therapies, are allowed) - Has chemotherapy-related anemia (hemoglobin < 11 g/dL) - No anemia known to be secondary to gastrointestinal bleeding or hemolysis - No anemia known to be secondary to vitamin B12 or folic acid deficiency + Vitamin B12 and folic acid deficiency must be ruled out if the mean corpuscular volume (MCV) is > 100 fL - No anemia secondary to chemotherapy-induced myelodysplastic syndromes - No primary hematologic disorder causing moderate to severe anemia (e.g., congenital dyserythropoietic anemia, homozygous hemoglobin S disease or compound heterozygous sickling states, or thalassemia major) - Carriers for these disease states are eligible - No first-degree relative with primary hemochromatosis (unless the patient has undergone HFE genotyping and was found to have at least one wild-type allele, while the proband in the family demonstrated to have either the common C282Y or H63D mutation) PATIENT CHARACTERISTICS: - ECOG performance status 0-2 - Ferritin > 20 mcg/L (i.e., not obviously iron deficient) - ALT or AST < 5 times upper limit of normal - Alert, mentally competent, and able to sign informed consent - Not pregnant or nursing - Negative pregnancy test - Fertile patients must use effective contraception during and for 3 months after completion of study treatment - Willing or able to be randomized and undergo study treatment - Willing or able to fill out quality-of-life forms - No uncontrolled hypertension (i.e., systolic blood pressure [BP] ≥ 180 mm Hg or diastolic BP ≥ 100 mm Hg) - No history of uncontrolled cardiac arrhythmias - No pulmonary embolism or deep venous thrombosis within the past year (unless the patient is on anticoagulation therapy and planning to continue it during study participation) - No known hypersensitivity to darbepoetin alfa, erythropoietin, mammalian cell-derived products, iron, or human albumin - No seizures within the past 3 months - No gastrointestinal conditions expected to cause significant impairment of oral iron, such as untreated celiac disease or amyloidosis involving the gut - Patients with celiac disease who are adhering to a gluten-free diet are eligible PRIOR CONCURRENT THERAPY: - See Disease Characteristics - More than 3 months since prior darbepoetin alfa, epoetin alfa, or any investigational forms of erythropoietin (e.g., gene-activated erythropoietin or novel erythropoiesis-stimulating protein) - More than 1 year since prior peripheral blood stem cell or bone marrow transplantation - More than 2 weeks since prior red blood cell transfusions - More than 14 days since prior major surgery - No prior gastrectomy or resection of > 100 cm of small intestine - Not planning to undergo stem cell or bone marrow transplantation within the next 6 months Anemia Leukemia Lymphoma Lymphoproliferative Disorder Multiple Myeloma and Plasma Cell Neoplasm Precancerous Condition Unspecified Adult Solid Tumor, Protocol Specific Lymphoma Leukemia Multiple Myeloma Neoplasms, Plasma Cell Precancerous Conditions Anemia Lymphoproliferative Disorders OBJECTIVES: Primary * To compare the effects of IV iron, oral iron, or placebo in combination with darbepoetin alfa on the hematopoietic response rate, defined as a hemoglobin increment of ≥ 2.0 g/dL from baseline or achievement of hemoglobin of ≥ 11 g/dL in the absence of red blood cell transfusions (RBC) in the preceding 28 days of the treatment period, in cancer patients with chemotherapy-associated anemia. --- C282Y --- --- H63D --- --- C282Y ---

Primary Outcomes

Description: Hematopoietic response was defined as Hemoglobin (Hb) increment of 2.0 g/dL from baseline or achievement of Hb >= 11 g/dL (whichever occurs first) in the absence of red blood cell transfusions during the preceding 28 days during the treatment period.

Measure: Hematopoietic Response Rate Defined as the Number of Participants Who Exhibit a Hematopoietic Response

Time: 16 Weeks

Secondary Outcomes

Measure: Percentage of Patients Maintaining an Average Hemoglobin Level Within the National Comprehensive Cancer Network (NCCN) Range (11-13 g/dL) Through Week 16, Once Achieving a Hemoglobin of ≥ 11 g/dL

Time: 16 Weeks

Measure: Incidence of Patients Receiving at Least One Red Blood Cell (RBC) Transfusions

Time: Week 1 to Week 16

Description: Value at 7 weeks minus value at baseline.

Measure: Mean Increment in Hemoglobin Level at Week 7

Time: Baseline and 7 weeks

Description: Value at 16 weeks minus value at baseline.

Measure: Mean Increment in Hemoglobin Level at Week 16

Time: Baseline and 16 weeks

Description: Hematopoietic response was defined as Hb increment of 2.0 g/dL from baseline or achievement of Hb >= 11 g/dL (whichever occurs first) in the absence of red blood cell transfusions during the preceding 28 days during the treatment period.

Measure: Time to Hematopoietic Response

Time: 16 weeks

Measure: Time to First Red Blood Cell (RBC) Transfusions

Time: 16 weeks

Description: Overall QOL item score range: 0 (Worst) to 10 (Best), ordinal. Change: score at 16 weeks minus score at baseline.

Measure: Change From Baseline in Overall Quality of Life (QOL) Score as Measured by the Linear Analogue Self Assessment (LASA)

Time: Baseline and 16 weeks

Description: SDS Scale range: 0 (Worst), 100 (Best), ordinal. Change: score at 16 weeks minus score at baseline. A clinically significant result will be defined as a shift of 10 points on a 0-100 point transformed scale between the average QOL scores of the 3 variants of iron therapy.

Measure: Change From Baseline in Quality of Life (QOL) Score as Measured by Symptom Distress Scale (SDS) at End of Study

Time: Baseline and 16 weeks

Description: Fatigue Now Scale range: 0 (No Fatigue) to 10 (Worst), ordinal. Change: score at 16 weeks minus score at baseline.

Measure: Change From Baseline in Quality of Life (QOL) Score as Measured by Brief Fatigue Inventory(BFI) Fatigue Now Scale at End of Study

Time: Baseline and 16 weeks

Description: FACT-AN Scale range: 0 (Worst) to 100 (Best), ordinal. Change: score at 16 weeks minus score at baseline. A clinically significant result will be defined as a shift of 10 points on a 0-100 point transformed scale between the average QOL scores of the 3 variants of iron therapy.

Measure: Change From Baseline in Quality of Life (QOL) Score as Measured by The Functional Assessment of Cancer Therapy-Anemia (FACT-An) at End of Study

Time: Baseline and 16 weeks

Measure: C-reactive Protein (CRP) Level at Week 1, Week 7 and Week 16

Time: 1 Week, 7 Weeks and 16 Weeks

Measure: Soluble Transferrin Receptor (sTfR)Level at Week 1, Week 7 and Week 16

Time: 1 week, 7 weeks and 16 weeks

Measure: Ferritin Level at Baseline, Week 7 and Week 16

Time: Baseline, 7 weeks and 16 weeks

Description: MCV is a measure of the average red blood cell volume.

Measure: Mean Corpuscular Volume (MCV) Level at Baseline, Week 7 and Week 16

Time: Baseline, 7 weeks and 16 weeks

Measure: Transferrin Saturation at Baseline, Week 7 and Week 16

Time: Baseline, 7 weeks and 16 weeks

19 Effects of Intravenous Injection of Erythropoietin on Hepcidin Pharmacokinetics in Healthy Volunteers

The aim of this study is to measure the variations of serum and urinary hepcidin levels following a single intravenous injection of erythropoietin in healthy volunteers. Hepcidin is a major regulator of iron homeostasis. It acts by binding on ferroportin, and limits cellular efflux of iron through enterocytes and macrophages. Anemia and hypoxia are known to modulate hepcidin synthesis. In these situations, erythropoietin synthesis is increased, so it can be postulated that erythropoietin could modulate hepcidin synthesis.

NCT00687518 Iron Metabolism Disorders Drug: Erythropoietin Drug: Placebo
MeSH: Metabolic Diseases Iron Metabolism Disorders

Inclusion Criteria: - healthy volunteers - male aged 18 - 30 - normal routine laboratory values - normal ECG - normal iron status Exclusion Criteria: - C282Y mutation of the HFE gene - alcohol or tobacco consumption Inclusion Criteria: - healthy volunteers - male aged 18 - 30 - normal routine laboratory values - normal ECG - normal iron status Exclusion Criteria: - C282Y mutation of the HFE gene - alcohol or tobacco consumption Iron Metabolism Disorders Metabolic Diseases Iron Metabolism Disorders null --- C282Y ---

Inclusion Criteria: - healthy volunteers - male aged 18 - 30 - normal routine laboratory values - normal ECG - normal iron status Exclusion Criteria: - C282Y mutation of the HFE gene - alcohol or tobacco consumption Inclusion Criteria: - healthy volunteers - male aged 18 - 30 - normal routine laboratory values - normal ECG - normal iron status Exclusion Criteria: - C282Y mutation of the HFE gene - alcohol or tobacco consumption Iron Metabolism Disorders Metabolic Diseases Iron Metabolism Disorders null --- C282Y --- --- C282Y ---

Primary Outcomes

Measure: serum hepcidin levels

Time: over 24 hours

Secondary Outcomes

Measure: urinary hepcidin levels

Time: over 24 hours

Measure: serum iron and ferritin levels

Time: over 24 hours

20 A Phase II Trial of the Safety and Efficacy of Iron Reduction by Phlebotomy in Recipients of Hematopoietic Stem Cell Transplants

Hypothesis: The reduction of total body iron by phlebotomy will be safe and feasible in the post-HSCT setting Iron overload is common after hematopoietic stem cell transplantation. It is associated with chronic liver disease, with increased rates of infection and decreased survival. Eligible, consenting patients will have once monthly phlebotomy procedures (500ml) for 12 months. SAFETY: At each visit, patients will have a comprehensive assessment prior to starting and after completing the phlebotomy. This assessment will include determination of pain at phlebotomy site, local infection and an assessment of symptoms of anemia including presyncope, fatigue and dyspnea. The patient's pulse, blood pressure, respiratory rate and temperature will also be determined before and following the phlebotomy. EFFICACY: Iron stores will be measured serially in each patient. Measurements will be performed prior to the start of phlebotomy, and at 6 months and 12 months following the start of the series of 12 phlebotomies. These evaluations will be undertaken regardless of the number of phlebotomies which the patient actually undergoes. Iron stores will be estimated by measuring serum ferritin and transferrin saturation levels. Total body iron will be estimated from hepatic and cardiac iron concentration as measured by magnetic resonance imaging (MRI). Gandon et al. (12) described a non-invasive technique using MRI to measure hepatic iron stores. Iron is a paramagnetic substance which causes local magnetic field inhomogeneities leading to dephasing and signal loss in MRI. Gradient echo sequences are most susceptible to their effects because they do not use a 180° refocusing pulse, unlike conventional spin-echo sequences. Gandon et al. used multiple gradient echo sequences, compared the signal in liver to adjacent muscle and used this ratio to correlate with hepatic iron levels measured on tissue biopsy samples using spectrophotometric analysis. Multiple sequences were used because the nomogram comparing the L/M signal ratio is linear over only a small concentration of tissue iron.

NCT00689182 Iron Overload Procedure: monthly phlebotomy x 12 months
MeSH: Iron Overload

Serum samples will also be collected at baseline to screen for the most common mutations of the HFE gene (C282Y mutation and H63D mutation) as hereditary hemochromatosis is common in the general population and may contribute to iron overload in HSCT recipients. --- C282Y ---

Primary Outcomes

Measure: Iron stores, total body iron

Time: 1 year

21 The Effect of the Dietary Supplement Protandim on Non-Alcoholic Steatohepatitis: A Randomized, Double Blind, Placebo-Controlled Study

The purpose of this study is to evaluate the effect of Protandim on the degree of liver injury after one year of supplementation. Protandim is a nutritional supplement composed of the following 5 botanical extracts: Bacopa Moniera extract, Milk Thistle extract, Ashwagandha powder, Green tea, and Turmeric extract. Protandim is commercially available and can be purchased without a prescription. Our findings could lead to a better understanding of the role of oxidative stress and antioxidant therapy in NASH and may ultimately help improve patient care. Hypothesis #1: Protandim will lead to a significant improvement in NAS compared to placebo. Hypothesis #2: Protandim will lead to a significant decrease in serum markers of oxidative stress and liver chemistry tests. Hypothesis #3: Protandim will lead to decreased levels of TNF- α compared to placebo.

NCT00977730 Non-Alcoholic Steatohepatitis Dietary Supplement: Protandim Dietary Supplement: Placebo
MeSH: Fatty Liver Non-alcoholic Fatty Liver Disease
HPO: Hepatic steatosis

7. Iron overload/hemochromatosis, as defined by the following: elevated transferrin saturation (greater than 45 percent) OR serum ferritin (> 300 microg/L in men or >200 microg/L in women), with one of the following: 1) presence of 3+ or 4+ stainable iron on liver biopsy (if obtained); or 2) Hemochromatosis gene testing showing homozygosity for C282Y or compound heterozygosity for C282Y/H63D (if obtained). --- C282Y ---

Primary Outcomes

Measure: Change in NAS at study completion in the Protandim group compared to the placebo group.

Time: 12 months

22 Impact of Host Iron Status and Iron Supplement Use on Growth and Viability of the Erythrocytic Stage of Plasmodium Falciparum

The purpose of this study is to perform laboratory based studies to determine if the growth and development of the malaria parasite is effected by iron status of its host (the person infected with the malaria parasite). Iron deficiency affects over 500 million people including many pregnant women and children from areas of the world that are plagued by malaria. Some population based studies have suggested that iron deficiency protects people from getting malaria and this has raised questions about the wisdom of public health policies that provide universal iron supplementation in countries where malaria is common. We will use red blood cells and sera from patients with iron deficiency anemia, hereditary hemochromatosis and normal individuals who are taking iron supplements to look at this question in a very systematic way. This study should provide information for or against a possible mechanism by which iron deficiency may affect the malaria parasite. The results will contribute to efforts to develop evidence-based public health policies on iron supplementation policies in malaria-endemic areas. There are three different types of individuals involved in this study (1) people with iron deficiency anemia who will be taking iron supplementation (2) people without iron deficiency anemia who will be taking iron supplementation and (3) people with a condition called hereditary hemochromatosis who have an excess of iron in their bodies.

NCT01027663 Iron Deficiency Anemia Malaria Dietary Supplement: Iron Supplement
MeSH: Malaria Anemia, Iron-Deficiency
HPO: Iron deficiency anemia

From the genotype standpoint, only patients homozygous for the C282Y and H63D mutations and those that are compound heterozygotes for C282Y/H63D will be enrolled. --- C282Y ---


23 Prospective Randomized Study Comparing the Effect of Phlebotomy and Lifestyle and Diet Advices vs Lifestyle and Diet Advices Only on Glycemia in Patients With Dysmetabolic Liversiderosis

Insulin resistance-associated hepatic iron overload (IR-HIO), also defined as dysmetabolic iron overload syndrome or dysmetabolic liversiderosis, is a common cause or iron overload in France, mainly in middle-age patients with increased serum ferritin levels associated with normal serum transferrin saturation, and normal serum iron concentration in the absence of other known cause of increased serum ferritin levels. Treatment includes a combination of dietary measures and physical activity to correct metabolic disorders. Phlebotomies seem to be beneficial when serum ferritin level is high. This study aims at comparing the effect of iron depletion (by phlebotomy) plus lifestyle and diet advices versus lifestyle and diet advices alone on blood glucose level and insulin sensitivity in subjects with IR-HIO in order to assess the benefits of phlebotomies on the reduction of risk of diabetes and cardiovascular associated complications.

NCT01045525 Liver Cirrhosis Iron Overload Procedure: Phlebotomy Behavioral: Lifestyle and diet advices
MeSH: Liver Cirrhosis Iron Overload
HPO: Cirrhosis Hepatic fibrosis

Inclusion Criteria: - Age over 18 - Signed written informed consent - Ferritin ≥ 450 µg/L and ≤ 1500 µg/L - Hepatic iron overload proved by MRI or histological biochemical measurement (Iron hepatic concentration ≥ 50 μmol/g) - At least one of the following criteria : - Body mass index > 25 kg/m² - Systolic blood pressure ≥ 140mmHg or diastolic blood pressure ≥ 90 mmHg or antihypertensive treatment - Abdominal obesity (waist measurement ≥ 94 cm for men and ≥ 80 cm for women) - Fasting triglyceridemia ≥ 1.7 mmol/L or triglyceride-lowering treatment - Fasting HDL cholesterol < 1.03 mmol/L for men and < 1.29 mmol/L for women or HDL cholesterol-elevating treatment - Fasting blood glycemia ≥ 5.6 mmol/L Exclusion Criteria: - Subjects deprived of their liberty by judicial or administrative decision - Pregnant women - Other causes of increased serum ferritin levels: - Inflammatory syndrome (CRP >10 mg/L) or inflammatory, immune or malignant diseases - Hyper-hemolysis - Alcohol consumption more than 210 g for men and 140 g for women per week within the year before inclusion - Haemochromatosis established by the C282Y homozygous genotype - Chronic hepatic cytolysis due to : viral infection (HBV, HCV), alcohol, hyperthyroid disease, celiac disease, drug or immune hepatitis - Increased serum ferritin levels - cataract syndrome (familial cataract or personal history of cataract before 50 years of age) - Low ceruloplasmin level - Porphyria (cutaneous signs) - Contraindication of phlebotomy - Haemoglobin <13 g/dL for men and <12g/dL for women (threshold established by the French Blood Agency) - Congestive heart failure or coronary heart disease - Hepatic failure (TP<60%), renal failure (GFR <50mL/min) or respiratory insufficiency (chronic dyspnea) - Poor venous system - Fasting blood glycemia > 7 mmol/L or type 1 or type 2 diabetes, treated or not - Use of drugs known to have anti-steatotic effects : metformin, thiazolidinedione Inclusion Criteria: - Age over 18 - Signed written informed consent - Ferritin ≥ 450 µg/L and ≤ 1500 µg/L - Hepatic iron overload proved by MRI or histological biochemical measurement (Iron hepatic concentration ≥ 50 μmol/g) - At least one of the following criteria : - Body mass index > 25 kg/m² - Systolic blood pressure ≥ 140mmHg or diastolic blood pressure ≥ 90 mmHg or antihypertensive treatment - Abdominal obesity (waist measurement ≥ 94 cm for men and ≥ 80 cm for women) - Fasting triglyceridemia ≥ 1.7 mmol/L or triglyceride-lowering treatment - Fasting HDL cholesterol < 1.03 mmol/L for men and < 1.29 mmol/L for women or HDL cholesterol-elevating treatment - Fasting blood glycemia ≥ 5.6 mmol/L Exclusion Criteria: - Subjects deprived of their liberty by judicial or administrative decision - Pregnant women - Other causes of increased serum ferritin levels: - Inflammatory syndrome (CRP >10 mg/L) or inflammatory, immune or malignant diseases - Hyper-hemolysis - Alcohol consumption more than 210 g for men and 140 g for women per week within the year before inclusion - Haemochromatosis established by the C282Y homozygous genotype - Chronic hepatic cytolysis due to : viral infection (HBV, HCV), alcohol, hyperthyroid disease, celiac disease, drug or immune hepatitis - Increased serum ferritin levels - cataract syndrome (familial cataract or personal history of cataract before 50 years of age) - Low ceruloplasmin level - Porphyria (cutaneous signs) - Contraindication of phlebotomy - Haemoglobin <13 g/dL for men and <12g/dL for women (threshold established by the French Blood Agency) - Congestive heart failure or coronary heart disease - Hepatic failure (TP<60%), renal failure (GFR <50mL/min) or respiratory insufficiency (chronic dyspnea) - Poor venous system - Fasting blood glycemia > 7 mmol/L or type 1 or type 2 diabetes, treated or not - Use of drugs known to have anti-steatotic effects : metformin, thiazolidinedione Liver Cirrhosis Iron Overload Liver Cirrhosis Iron Overload Non applicable --- C282Y ---

Inclusion Criteria: - Age over 18 - Signed written informed consent - Ferritin ≥ 450 µg/L and ≤ 1500 µg/L - Hepatic iron overload proved by MRI or histological biochemical measurement (Iron hepatic concentration ≥ 50 μmol/g) - At least one of the following criteria : - Body mass index > 25 kg/m² - Systolic blood pressure ≥ 140mmHg or diastolic blood pressure ≥ 90 mmHg or antihypertensive treatment - Abdominal obesity (waist measurement ≥ 94 cm for men and ≥ 80 cm for women) - Fasting triglyceridemia ≥ 1.7 mmol/L or triglyceride-lowering treatment - Fasting HDL cholesterol < 1.03 mmol/L for men and < 1.29 mmol/L for women or HDL cholesterol-elevating treatment - Fasting blood glycemia ≥ 5.6 mmol/L Exclusion Criteria: - Subjects deprived of their liberty by judicial or administrative decision - Pregnant women - Other causes of increased serum ferritin levels: - Inflammatory syndrome (CRP >10 mg/L) or inflammatory, immune or malignant diseases - Hyper-hemolysis - Alcohol consumption more than 210 g for men and 140 g for women per week within the year before inclusion - Haemochromatosis established by the C282Y homozygous genotype - Chronic hepatic cytolysis due to : viral infection (HBV, HCV), alcohol, hyperthyroid disease, celiac disease, drug or immune hepatitis - Increased serum ferritin levels - cataract syndrome (familial cataract or personal history of cataract before 50 years of age) - Low ceruloplasmin level - Porphyria (cutaneous signs) - Contraindication of phlebotomy - Haemoglobin <13 g/dL for men and <12g/dL for women (threshold established by the French Blood Agency) - Congestive heart failure or coronary heart disease - Hepatic failure (TP<60%), renal failure (GFR <50mL/min) or respiratory insufficiency (chronic dyspnea) - Poor venous system - Fasting blood glycemia > 7 mmol/L or type 1 or type 2 diabetes, treated or not - Use of drugs known to have anti-steatotic effects : metformin, thiazolidinedione Inclusion Criteria: - Age over 18 - Signed written informed consent - Ferritin ≥ 450 µg/L and ≤ 1500 µg/L - Hepatic iron overload proved by MRI or histological biochemical measurement (Iron hepatic concentration ≥ 50 μmol/g) - At least one of the following criteria : - Body mass index > 25 kg/m² - Systolic blood pressure ≥ 140mmHg or diastolic blood pressure ≥ 90 mmHg or antihypertensive treatment - Abdominal obesity (waist measurement ≥ 94 cm for men and ≥ 80 cm for women) - Fasting triglyceridemia ≥ 1.7 mmol/L or triglyceride-lowering treatment - Fasting HDL cholesterol < 1.03 mmol/L for men and < 1.29 mmol/L for women or HDL cholesterol-elevating treatment - Fasting blood glycemia ≥ 5.6 mmol/L Exclusion Criteria: - Subjects deprived of their liberty by judicial or administrative decision - Pregnant women - Other causes of increased serum ferritin levels: - Inflammatory syndrome (CRP >10 mg/L) or inflammatory, immune or malignant diseases - Hyper-hemolysis - Alcohol consumption more than 210 g for men and 140 g for women per week within the year before inclusion - Haemochromatosis established by the C282Y homozygous genotype - Chronic hepatic cytolysis due to : viral infection (HBV, HCV), alcohol, hyperthyroid disease, celiac disease, drug or immune hepatitis - Increased serum ferritin levels - cataract syndrome (familial cataract or personal history of cataract before 50 years of age) - Low ceruloplasmin level - Porphyria (cutaneous signs) - Contraindication of phlebotomy - Haemoglobin <13 g/dL for men and <12g/dL for women (threshold established by the French Blood Agency) - Congestive heart failure or coronary heart disease - Hepatic failure (TP<60%), renal failure (GFR <50mL/min) or respiratory insufficiency (chronic dyspnea) - Poor venous system - Fasting blood glycemia > 7 mmol/L or type 1 or type 2 diabetes, treated or not - Use of drugs known to have anti-steatotic effects : metformin, thiazolidinedione Liver Cirrhosis Iron Overload Liver Cirrhosis Iron Overload Non applicable --- C282Y --- --- C282Y ---

Primary Outcomes

Measure: Fasting blood glycemia (T0 of Oral Glucose Tolerance Test)

Time: 12 months

Secondary Outcomes

Measure: Rate of Body mass index > 25 kg/m²

Time: 12 months

Measure: Rate of systolic blood pressure ≥ 130mmHg or diastolic blood pressure ≥ 85 mmHg or antihypertensive treatment

Time: 12 months

Measure: Rate of abdominal obesity (waist measurement ≥ 94 cm for men and ≥ 80 cm for women)

Time: 12 months

Measure: Rate of fasting triglyceridemia ≥ 1.7 mmol/L or triglyceride-lowering treatment

Time: 12 months

Measure: Rate of fasting HDL cholesterol < 1.03 mmol/L for men and < 1.29 mmol/L for women or HDL cholesterol-elevating treatment

Time: 12 months

Measure: Rate of fasting glycemia ≥ 5.6 mmol/L

Time: 12 months

Measure: HbA1c value

Time: 12 months

Measure: Quality of life estimated with SF36 form and tolerance to treatment

Time: 12 months

Measure: Insulinoresistance indexes calculated at T0 and T30 min of Oral Glucose Tolerance Test (OGTT)

Time: 12 months

Measure: Biological markers: CRP, hyaluronic acid, fibrometer

Time: 12 months

Description: Two dimensional (2D) speckle tracking echocardiography (STE)

Measure: myocardial deformation

Time: 12 months

24 Effects of Blood Letting on Insulin Sensitivity and Blood Pressure in Patients With Metabolic Syndrome: A Randomized Controlled Trial

Metabolic syndrome (MS) has an increasing prevalence worldwide and there is an urgent need for improvement of medical treatment. In traditional medicine phlebotomy (blood letting) is a recommended treatment for subjects with obesity and vascular disease. Recent studies showed that blood letting with iron depletion may improve insulin sensitivity in patients with diabetes mellitus. The investigators aimed to test if traditional blood letting has beneficial effects in patients with MS. A randomized trial with a sample size of 64 self-referred MS patients was conducted. Patients in the blood letting group were allocated to blood letting intervention and the control group was offered a later treatment (waiting list). In the intervention group 300-400 ml of venous blood were withdrawn at day 1 and after 4 weeks. Primary outcomes were the change of systolic blood pressure and of insulin sensitivity as measured by HOMA-Index.

NCT01328210 Metabolic Syndrome Procedure: blood letting
MeSH: Metabolic Syndrome Syndrome

Inclusion Criteria: - 25-70 years of age - given diagnosis of metabolic syndrome Exclusion Criteria: - clinically significant hepatic, neurological, endocrinologic, or other major systemic or inflammatory disease, including malignancy - known history of hemochromatosis, or presence of the Cys282Tyr mutation - history of drug or alcohol abuse - manifest cardiac disease - history of disturbances in iron balance (e.g., hemosiderosis from any cause, atransferrinemia) - preexisting anemia Inclusion Criteria: - 25-70 years of age - given diagnosis of metabolic syndrome Exclusion Criteria: - clinically significant hepatic, neurological, endocrinologic, or other major systemic or inflammatory disease, including malignancy - known history of hemochromatosis, or presence of the Cys282Tyr mutation - history of drug or alcohol abuse - manifest cardiac disease - history of disturbances in iron balance (e.g., hemosiderosis from any cause, atransferrinemia) - preexisting anemia Metabolic Syndrome Metabolic Syndrome Syndrome null --- Cys282Tyr ---

Inclusion Criteria: - 25-70 years of age - given diagnosis of metabolic syndrome Exclusion Criteria: - clinically significant hepatic, neurological, endocrinologic, or other major systemic or inflammatory disease, including malignancy - known history of hemochromatosis, or presence of the Cys282Tyr mutation - history of drug or alcohol abuse - manifest cardiac disease - history of disturbances in iron balance (e.g., hemosiderosis from any cause, atransferrinemia) - preexisting anemia Inclusion Criteria: - 25-70 years of age - given diagnosis of metabolic syndrome Exclusion Criteria: - clinically significant hepatic, neurological, endocrinologic, or other major systemic or inflammatory disease, including malignancy - known history of hemochromatosis, or presence of the Cys282Tyr mutation - history of drug or alcohol abuse - manifest cardiac disease - history of disturbances in iron balance (e.g., hemosiderosis from any cause, atransferrinemia) - preexisting anemia Metabolic Syndrome Metabolic Syndrome Syndrome null --- Cys282Tyr --- --- Cys282Tyr ---

Primary Outcomes

Description: Glucose and insulin are measured on the basis of overnight fasting blood samples and Insulin sensitivity calculated according to HOMA-Index

Measure: insulin sensitivity

Time: change from baseline at 6 weeks

Description: Blood pressure is measured twice after 5 minutes rest in the sitting position by sphygmomanometry

Measure: systolic blood pressure

Time: change from baseline at 6 weeks

Secondary Outcomes

Measure: diastolic blood pressure

Time: change from baseline at 6 weeks

Measure: HbA1c

Time: change from baseline at 6 weeks

Measure: blood lipids

Time: change from baseline at 6 weeks

Measure: serum ferritin

Time: change from baseline at 6 weeks

Measure: adiponectin

Time: change from baseline at 6 weeks

Measure: blood count

Time: change from baseline at 6 weeks

Measure: serum iron

Time: change from baseline at 6 weeks

Measure: hs-CRP

Time: change from baseline at 6 weeks

Measure: pulse rate

Time: change from baseline at 6 weeks

Measure: serum glucose

Time: change from baseline at 6 weeks

25 Erythrocytapheresis Versus Phlebotomy as Maintenance Therapy in Patients With Hereditary Hemochromatosis; a Randomised, Single Blinded Sequential, Cross-over Trial

Hereditary hemochromatosis (HH) is a genetic disorder of iron metabolism, resulting in excessive iron overload. Phlebotomy is currently the standard therapy. More recently Therapeutic Erythrocytapheresis (TE) has become a new therapeutic modality, which potentially offers a more efficient method to remove iron overload with fewer procedures.In the proposed clinical trial the investigators will examine whether TE can keep the ferritin levels in patients requiring maintenance therapy below 50 microg/L, with minimally half the number of treatment procedures when compared to current standard therapy by P.

NCT01398644 Hereditary Hemochromatosis Other: Phlebotomy and erythrocytapheresis
MeSH: Hemochromatosis

Inclusion Criteria: - homozygous for C282Y - currently treated with phlebotomy as maintenance therapy for at least 6 month - ferritin level between 30-50 micog/L - age 18 years an older - weight more than 50 kg - signed informed consent - willingness to fill out additional questionnaires at three points in time Exclusion Criteria: - chelating therapy - forced dietary regime - aged below 18 years - excessive overweight ( BMI more than 35) - pregnancy Inclusion Criteria: - homozygous for C282Y - currently treated with phlebotomy as maintenance therapy for at least 6 month - ferritin level between 30-50 micog/L - age 18 years an older - weight more than 50 kg - signed informed consent - willingness to fill out additional questionnaires at three points in time Exclusion Criteria: - chelating therapy - forced dietary regime - aged below 18 years - excessive overweight ( BMI more than 35) - pregnancy Hereditary Hemochromatosis Hemochromatosis The research population exists of patients with HH ( by genetic analysis confirmed as homozygous for C282Y) living in south-east of the Netherlands and currently treated with phlebotomy as maintenance treatment to keep their serum ferritin levels < 50 ug/l. --- C282Y ---

Inclusion Criteria: - homozygous for C282Y - currently treated with phlebotomy as maintenance therapy for at least 6 month - ferritin level between 30-50 micog/L - age 18 years an older - weight more than 50 kg - signed informed consent - willingness to fill out additional questionnaires at three points in time Exclusion Criteria: - chelating therapy - forced dietary regime - aged below 18 years - excessive overweight ( BMI more than 35) - pregnancy Inclusion Criteria: - homozygous for C282Y - currently treated with phlebotomy as maintenance therapy for at least 6 month - ferritin level between 30-50 micog/L - age 18 years an older - weight more than 50 kg - signed informed consent - willingness to fill out additional questionnaires at three points in time Exclusion Criteria: - chelating therapy - forced dietary regime - aged below 18 years - excessive overweight ( BMI more than 35) - pregnancy Hereditary Hemochromatosis Hemochromatosis The research population exists of patients with HH ( by genetic analysis confirmed as homozygous for C282Y) living in south-east of the Netherlands and currently treated with phlebotomy as maintenance treatment to keep their serum ferritin levels < 50 ug/l. --- C282Y --- --- C282Y ---

Inclusion Criteria: - homozygous for C282Y - currently treated with phlebotomy as maintenance therapy for at least 6 month - ferritin level between 30-50 micog/L - age 18 years an older - weight more than 50 kg - signed informed consent - willingness to fill out additional questionnaires at three points in time Exclusion Criteria: - chelating therapy - forced dietary regime - aged below 18 years - excessive overweight ( BMI more than 35) - pregnancy Inclusion Criteria: - homozygous for C282Y - currently treated with phlebotomy as maintenance therapy for at least 6 month - ferritin level between 30-50 micog/L - age 18 years an older - weight more than 50 kg - signed informed consent - willingness to fill out additional questionnaires at three points in time Exclusion Criteria: - chelating therapy - forced dietary regime - aged below 18 years - excessive overweight ( BMI more than 35) - pregnancy Hereditary Hemochromatosis Hemochromatosis The research population exists of patients with HH ( by genetic analysis confirmed as homozygous for C282Y) living in south-east of the Netherlands and currently treated with phlebotomy as maintenance treatment to keep their serum ferritin levels < 50 ug/l. --- C282Y --- --- C282Y --- --- C282Y ---

Primary Outcomes

Measure: The difference in number of required treatments and the interval between treatments per year to keep the serum ferritin levels between 30-50 microg/L

Time: one year after first phlebotomy treatment and one year after first erythrocytapheresis treatment

26 Effect of Curcumin on Iron Metabolism in Healthy Volunteer

The purpose of this study is to determine the impact of curcumin, administrated orally, on iron metabolism in healthy volunteers. Iron metabolism will be describe by hepcidin expression that the investigators observed in vitro and serum hepcidin levels.

NCT01489592 Healthy Volunteers Drug: curcuma longa

In vitro: the coculture model that we previously developed to analyze endogenous hepcidin expression, and human hepatic cells line (HepG2) stimulated or not by IL-6 which governs the STAT3 pathway, transfected with gene reporter constructs containing hepcidin promoter.. Inclusion Criteria: - Body mass index between 18 et 25 Kg/m² - Non smoker - No swallowing disorders - Normal clinical exam - Normal ECG - Normal values for routine biological tests : serum iron, transferrin saturation,, hemogram ferritin, C Reactive Protein, AST, ALT, HDL and LDL cholesterol, triglycerides - No C282Y mutation within the HFE gene - Affiliation to social security - Written informed consent obtained Exclusion Criteria: - Chronic or evolutive disease - Infection during the 7 days before each sequence - Drug or alcohol (>30g) abuse - Current treatment - Known food allergy - stay at altitude (> 1500m) in 2 months - Positive serology for hepatitis B or C virus or HIV. - Transfusion or blood donation during the last three months. --- C282Y ---

Inclusion Criteria: - Body mass index between 18 et 25 Kg/m² - Non smoker - No swallowing disorders - Normal clinical exam - Normal ECG - Normal values for routine biological tests : serum iron, transferrin saturation,, hemogram ferritin, C Reactive Protein, AST, ALT, HDL and LDL cholesterol, triglycerides - No C282Y mutation within the HFE gene - Affiliation to social security - Written informed consent obtained Exclusion Criteria: - Chronic or evolutive disease - Infection during the 7 days before each sequence - Drug or alcohol (>30g) abuse - Current treatment - Known food allergy - stay at altitude (> 1500m) in 2 months - Positive serology for hepatitis B or C virus or HIV. - Transfusion or blood donation during the last three months. --- C282Y ---

Primary Outcomes

Measure: Maximal variation of serum hepcidin level after oral administration of curcumin

Time: within 48 hours after administration of curcumin

Secondary Outcomes

Description: Iron, ferritin, transferrin, transferrin saturation

Measure: Plasmatic iron bioavailability

Time: 30min, 1H, 2H, 3H, 4H, 6H, 8H, 12H, 24H et 48H

Description: In vitro: the coculture model that we previously developed to analyze endogenous hepcidin expression, and human hepatic cells line (HepG2) stimulated or not by IL-6 which governs the STAT3 pathway, transfected with gene reporter constructs containing hepcidin promoter.

Measure: Evaluation of the inhibitory activity of volunteers's serum on hepcidin expression by hepatocytes

Time: 30min, 1h, 2h, 3h, 4h, 6h, 8h, 12h, 24h

27 Proton Pump Inhibitors in the Prevention of Iron Reaccumulation in Patient With Hereditary Hemochromatosis

Hereditary Hemochromatosis (HH) is a genetic disorder of iron metabolism, resulting in excessive iron overload causing damage of different important organs like heart, liver, pancreas and joints. Complications and symptoms can regress by intensive treatment reducing the iron overload stores.Different genes have been identified playing a role in the pathophysiology of iron overload. A clinically important HFE gene mutation is the C282Y, located on chromosome 6. Phlebotomy is currently the standard therapy which consists of removal of 500 ml whole blood weekly, representing a loss of 250 mg iron. In naive patients between 20 to 100 phlebotomies are required to reduce the serum ferritine levels to 50 μg/L. Thereafter, a lifelong maintenance therapy of 3 to 6 phlebotomies yearly is needed. For absorption, dietary iron ( 70%) is reduced by gastric acid form the ferric (Fe3+) to the ferrous form (Fe2+). Recently, in an observational open study, Hutchinson et al. found that HH patients treated with proton pump inhibitors (PPI) needed fewer phlebotomies, resulting in a drop of 2.5 (SEM 0.25) to 0.5 (SEM 0.25) liter per year. Research question: The primary objective is to determine the effectiveness and cost effectiveness of PPI's compared to standard phlebotomy therapy in the prevention of iron overload in HH patients. Multi-center trial in two hospitals in the South of Limburg (Atrium medical Center, Maastricht university medical center ) and hospital in Belgium (University Hospital Gasthuisberg). The study will be conducted in randomised double blind manner. The follow up will be one year. Patients are randomized either for the group receiving a PPI or a placebo. Every 2 month the ferritin level is measured and decided if the patient need a phlebotomy (Ferritin >100 µg/L).

NCT01524757 Hemochromatosis Drug: Pantoprazole
MeSH: Hemochromatosis

A clinically important HFE gene mutation is the C282Y, located on chromosome 6. --- C282Y ---

Inclusion Criteria: - Patients with hereditary hemochromatosis (HH), homozygous for C282Y, currently treated with phlebotomy as maintenance therapy for at least 12 months with ≥ 3 phlebotomies per year. --- C282Y ---

Primary Outcomes

Measure: the total number of phlebotomies for the group taking PPI treatment compared to the group taking placebo will be the primary endpoint of the study.

Time: 12 months

Secondary Outcomes

Measure: number of participants with side effects

Time: 12 months

28 Clinical, Biological, Genetic and Functional Characterization of Rare Iron Overload Phenotypes Associated With Hepcidin Deficiency Except C282Y Homozygosity.

Chronic iron overload is responsible for morbidity and mortality. There are many genetic and acquired causes. One of them is an hepcidin deficiency. Hepcidin is the regulating hormone for iron. The study explores this specific cause, and aim to characterize this iron overload in term of clinical, biological, genetic and functional specificities.

NCT01541813 Rare Iron Overloads Except C282Y Homozygosity
MeSH: Iron Overload

Clinical, Biological, Genetic and Functional Characterization of Rare Iron Overload Phenotypes Associated With Hepcidin Deficiency Except C282Y Homozygosity.. Rare Iron Overloads Except C282Y Homozygosity : Description and Characterization. --- C282Y ---

Clinical, Biological, Genetic and Functional Characterization of Rare Iron Overload Phenotypes Associated With Hepcidin Deficiency Except C282Y Homozygosity.. Rare Iron Overloads Except C282Y Homozygosity : Description and Characterization. --- C282Y --- --- C282Y ---

Non inclusion criteria: - HFE hemochromatosis: C282Y/C282Y homozygosity - Treatment by iterative phlebotomies (more than 2 phlebotomies) - Hematological diseases with dyserythropoiesis and/or repeated transfusions - Low haptoglobin level, suggesting chronic hemolysis or myelodysplasia - Long-term iron oral and/or parenteral supplementation Inclusion criteria: - Biological profile suggesting hepcidin deficiency: - high serum iron (> 25μmol / l) checked at least 2 times. --- C282Y ---

Non inclusion criteria: - HFE hemochromatosis: C282Y/C282Y homozygosity - Treatment by iterative phlebotomies (more than 2 phlebotomies) - Hematological diseases with dyserythropoiesis and/or repeated transfusions - Low haptoglobin level, suggesting chronic hemolysis or myelodysplasia - Long-term iron oral and/or parenteral supplementation Rare Iron Overloads Except C282Y Homozygosity Iron Overload One of chronic iron overload profiles is a deficit in hepcidin. --- C282Y ---

Non inclusion criteria: - HFE hemochromatosis: C282Y/C282Y homozygosity - Treatment by iterative phlebotomies (more than 2 phlebotomies) - Hematological diseases with dyserythropoiesis and/or repeated transfusions - Low haptoglobin level, suggesting chronic hemolysis or myelodysplasia - Long-term iron oral and/or parenteral supplementation Rare Iron Overloads Except C282Y Homozygosity Iron Overload One of chronic iron overload profiles is a deficit in hepcidin. --- C282Y --- --- C282Y ---

The main objective of this study is the clinical, biological, genetic and functional characterization of rare iron overload phenotypes associated with hepcidin deficiency except C282Y homozygosity. --- C282Y ---


29 Effects of Phlebotomy on Insulin Sensitivity in Insulin Resistance-associated Hepatic Iron Overload Patients

The purpose of this study is to evaluate efficacy of phlebotomy on insulin sensitivity as evaluated by euglycemic-hyperinsulinic clamp in insulin resistance-associated hepatic iron overload patients.

NCT01572818 Insulin Resistance Iron Overload Procedure: phlebotomy Behavioral: dietary and lifestyle counseling
MeSH: Insulin Resistance Iron Overload
HPO: Insulin resistance

Inclusion Criteria: - Age between 18 and 70 years - Ferritin between 450 and 1000 µg/L - Hepatic iron overload proved by MRI (CHF >36 µmol/g) - Body mass index > 25 kg/m² - Fasting glycemia <1,26 g/L - HbA1c < 6,5% - Signed written and informed consent Exclusion Criteria: - Other causes of hyperferritinemia: - Inflammatory syndrome (CRP >10 mg/L) or inflammatory, immune or malignant diseases - Hyperferritinemia-cataract syndrome (familial cataract or personal history of cataract before 50 years old) - Low ceruloplasmin level - Porphyria (cutaneous signs) - Haemochromatosis established by the genotype (C282Y homozygous or C282Y/H63D coumpound heterozygous genotypes) - Contraindication of phlebotomy - Haemoglobin <13,5 g/dL (threshold established by the Etablissement Français du Sang) - Heart failure or coronary heart diseases - Hepatic failure, renal (GFR <50mL/min) or respiratory insufficiency (chronic dyspnea) - Poor venous system - Viral, immune, genetic, vascular, malignant or toxic chronic hepatic disease - Alcohol consumption more than 21 doses per week during 5 years or more - Type 1 or type 2 diabetes - Oral anti-diabetic, corticoids or immune suppressor drugs - Hepatic severe disease - Claustrophobia, having a pace-maker or intracerebral clips - Subjects deprived of their liberty by judicial or administrative decision, subjects that are not affiliated to social security or topics exclusion period of a previous study Inclusion Criteria: - Age between 18 and 70 years - Ferritin between 450 and 1000 µg/L - Hepatic iron overload proved by MRI (CHF >36 µmol/g) - Body mass index > 25 kg/m² - Fasting glycemia <1,26 g/L - HbA1c < 6,5% - Signed written and informed consent Exclusion Criteria: - Other causes of hyperferritinemia: - Inflammatory syndrome (CRP >10 mg/L) or inflammatory, immune or malignant diseases - Hyperferritinemia-cataract syndrome (familial cataract or personal history of cataract before 50 years old) - Low ceruloplasmin level - Porphyria (cutaneous signs) - Haemochromatosis established by the genotype (C282Y homozygous or C282Y/H63D coumpound heterozygous genotypes) - Contraindication of phlebotomy - Haemoglobin <13,5 g/dL (threshold established by the Etablissement Français du Sang) - Heart failure or coronary heart diseases - Hepatic failure, renal (GFR <50mL/min) or respiratory insufficiency (chronic dyspnea) - Poor venous system - Viral, immune, genetic, vascular, malignant or toxic chronic hepatic disease - Alcohol consumption more than 21 doses per week during 5 years or more - Type 1 or type 2 diabetes - Oral anti-diabetic, corticoids or immune suppressor drugs - Hepatic severe disease - Claustrophobia, having a pace-maker or intracerebral clips - Subjects deprived of their liberty by judicial or administrative decision, subjects that are not affiliated to social security or topics exclusion period of a previous study Insulin Resistance Iron Overload Insulin Resistance Iron Overload The main objective of this study is to evaluate in patients with HSD effects of treatment with phlebotomy rules with lifestyle and dietary rules versus lifestyle modifications alone on peripheral insulin resistance (assessed by hyperinsulinemic clamp). --- C282Y ---

Inclusion Criteria: - Age between 18 and 70 years - Ferritin between 450 and 1000 µg/L - Hepatic iron overload proved by MRI (CHF >36 µmol/g) - Body mass index > 25 kg/m² - Fasting glycemia <1,26 g/L - HbA1c < 6,5% - Signed written and informed consent Exclusion Criteria: - Other causes of hyperferritinemia: - Inflammatory syndrome (CRP >10 mg/L) or inflammatory, immune or malignant diseases - Hyperferritinemia-cataract syndrome (familial cataract or personal history of cataract before 50 years old) - Low ceruloplasmin level - Porphyria (cutaneous signs) - Haemochromatosis established by the genotype (C282Y homozygous or C282Y/H63D coumpound heterozygous genotypes) - Contraindication of phlebotomy - Haemoglobin <13,5 g/dL (threshold established by the Etablissement Français du Sang) - Heart failure or coronary heart diseases - Hepatic failure, renal (GFR <50mL/min) or respiratory insufficiency (chronic dyspnea) - Poor venous system - Viral, immune, genetic, vascular, malignant or toxic chronic hepatic disease - Alcohol consumption more than 21 doses per week during 5 years or more - Type 1 or type 2 diabetes - Oral anti-diabetic, corticoids or immune suppressor drugs - Hepatic severe disease - Claustrophobia, having a pace-maker or intracerebral clips - Subjects deprived of their liberty by judicial or administrative decision, subjects that are not affiliated to social security or topics exclusion period of a previous study Inclusion Criteria: - Age between 18 and 70 years - Ferritin between 450 and 1000 µg/L - Hepatic iron overload proved by MRI (CHF >36 µmol/g) - Body mass index > 25 kg/m² - Fasting glycemia <1,26 g/L - HbA1c < 6,5% - Signed written and informed consent Exclusion Criteria: - Other causes of hyperferritinemia: - Inflammatory syndrome (CRP >10 mg/L) or inflammatory, immune or malignant diseases - Hyperferritinemia-cataract syndrome (familial cataract or personal history of cataract before 50 years old) - Low ceruloplasmin level - Porphyria (cutaneous signs) - Haemochromatosis established by the genotype (C282Y homozygous or C282Y/H63D coumpound heterozygous genotypes) - Contraindication of phlebotomy - Haemoglobin <13,5 g/dL (threshold established by the Etablissement Français du Sang) - Heart failure or coronary heart diseases - Hepatic failure, renal (GFR <50mL/min) or respiratory insufficiency (chronic dyspnea) - Poor venous system - Viral, immune, genetic, vascular, malignant or toxic chronic hepatic disease - Alcohol consumption more than 21 doses per week during 5 years or more - Type 1 or type 2 diabetes - Oral anti-diabetic, corticoids or immune suppressor drugs - Hepatic severe disease - Claustrophobia, having a pace-maker or intracerebral clips - Subjects deprived of their liberty by judicial or administrative decision, subjects that are not affiliated to social security or topics exclusion period of a previous study Insulin Resistance Iron Overload Insulin Resistance Iron Overload The main objective of this study is to evaluate in patients with HSD effects of treatment with phlebotomy rules with lifestyle and dietary rules versus lifestyle modifications alone on peripheral insulin resistance (assessed by hyperinsulinemic clamp). --- C282Y --- --- H63D --- --- C282Y ---

Primary Outcomes

Measure: Glucose Infusion Rate by euglycemic-hyperinsulinic clamp

Time: 6 months

Secondary Outcomes

Measure: hepatic parameters

Time: 6 months

Description: IL-6, TNF alpha, CRP

Measure: inflammation markers

Time: 6 months

Description: adiponectin, PAI1, leptin

Measure: Adipokins markers

Time: 6 months

Measure: SHBG

Time: 6 months

Measure: HOMA-IR

Time: 6 months

Description: transaminase (ALT, AST), gamma GT

Measure: Hepatic iron overload (MRI)

Time: 6 months

Measure: Abdominal and sub-cutaneous fat surface (MRI)

Time: 6 months

Description: serum iron, ferritin, saturation of transferrin

Measure: iron parameters

Time: at 6 months

Description: HDL-c, LDL-c, triglycerides

Measure: lipid profile

Time: at 6 months

30 Mi-Iron - Moderately Increased Iron - is Reducing Iron Overload Necessary?

Haemochromatosis is a preventable genetic iron overload disorder. Untreated, it can shorten life due mainly to liver cirrhosis and cancer. It can be prevented by blood donation to maintain normal iron levels. It is unclear, however, whether treatment is necessary when individuals have moderate elevation of iron in the body. This research project will study the effects of treatment in this group by assessing a number of scans, questionnaires and blood tests in treated and untreated individuals.

NCT01631708 Hereditary Haemochromatosis Procedure: Erythrocytapheresis Procedure: Plasmapheresis
MeSH: Hemochromatosis Iron Overload

To assess oxidative stress, we will measure F2-isoprostanes, a validated marker of cellular lipid oxidative damage, in urine and blood.. Inclusion Criteria: 1. HFE C282Y homozygous. --- C282Y ---

Exclusion Criteria: 1. HH due to genotypes other than HFE C282Y homozygosity. --- C282Y ---

Inclusion Criteria: 1. HFE C282Y homozygous. --- C282Y ---

Primary Outcomes

Description: Modified Fatigue Impact Scale (MFIS). The MFIS is a shortened version of the Fatigue Impact Scale. This 21-item scale can be self completed and measures the impact of fatigue on physical, cognitive and psychosocial functioning. Each item is scored from 0 (never) to 4 (almost always) resulting in a score from 0-84. In addition, physical (0-36), cognitive (0-40) and psychosocial (0-8) subscale scores can be derived.

Measure: Fatigue

Time: Clinically and statistically significant change in measures taken at baseline and at the end of treatment will be compared. Patients will have approximately 6 third weekly treatments however this will vary depending on initial SF.

Secondary Outcomes

Description: Liver fibrosis will be assessed using Hepascore and Fibrometer (blood tests) and transient elastography (ultrasound).

Measure: Change in markers of liver fibrosis

Time: Clinically and statistically significant change in measures taken at baseline and at the end of treatment will be compared. Patients will have on average 6 third weekly treatments (15 weeks).

Description: Medical Outcomes Study 36-item short form (SF36). As there are no specific quality of life tools available for HH, we will use this very widely used generic tool that has been used in a number of HH studies. This tool covers eight dimensions of health and wellbeing. One study found that individuals seen in a HH clinic and who had no clinical symptoms had significantly lower scores on a number of dimensions of the SF36 compared to population norms.

Measure: Quality of life

Time: Clinically and statistically significant change in measures taken at baseline and at the end of treatment will be compared. Patients will have on average 6 third weekly treatments (15 weeks).

Description: The Hospital Anxiety and Depression Scale (HADS) is a brief self-report measure designed to screen for anxiety symptoms and depression symptoms in a hospital setting. It is composed of two seven-item subscales, the Anxiety (HADS-A) and Depression (HADS-D) subscales, and a 14-item total scale (HADS-T). Participants use a four-point Likert-type scale to rate how they have felt in the past week. It has been found to be valid and reliable in various populations.

Measure: Depression and Anxiety

Time: Clinically and statistically significant change in measures taken at baseline and at the end of treatment will be compared. Patients will have on average 6 third weekly treatments (15 weeks).

Description: The presence and impact of arthritis will be measured by the Arthritis Impact Measurement Scales 2 short form. This is a 24 item validated scale that assesses the impact of arthritis on the individual over the past four weeks. We will also ascertain the use of arthritis medication at baseline and end of erythrocytapheresis/sham erythrocytapheresis.

Measure: Arthritis

Time: Clinically and statistically significant change in measures taken at baseline and at the end of treatment will be compared. Patients will have on average 6 third weekly treatments (15 weeks).

Description: To assess oxidative stress, we will measure F2-isoprostanes, a validated marker of cellular lipid oxidative damage, in urine and blood.

Measure: Markers of oxidative stress

Time: Clinically and statistically significant change in measures taken at baseline and at the end of treatment will be compared. Patients will have on average 6 third weekly treatments (15 weeks).

31 Ezetimibe Versus Placebo in the Treatment of Non-alcoholic Steatohepatitis

Nonalcoholic fatty liver disease (NAFLD) represents a spectrum of diseases ranging from simple steatosis to nonalcoholic steatohepatitis (NASH), the progressive form of liver disease that can lead to cirrhosis and liver-related mortality in persons who drink little or no alcohol. Nonalcoholic steatohepatitis (NASH) represents the more severe end of this spectrum and is characterized by steatosis, ballooning degeneration and lobular inflammation with or without fibrosis. The etiology of NASH is not completely understood, but it is often associated with obesity, type 2 diabetes, hyperlipidemia and insulin resistance. Lipotoxicity, insulin resistance and oxidative stress appear to be central to the pathogenesis of NASH. Currently, there is no FDA approved treatment for NAFLD/NASH. Weight loss and exercise are the recommended but often difficult maintain these lifestyle changes in the long term and therefore therapeutic agents have been investigated. Ezetimibe is an LDL lowering agent that works through inhibition of the fat absorption from the small intestine. In this study, we propose to treat 50 patients with NASH with either Ezetimibe or placebo for 24 weeks. After an initial evaluation for insulin sensitivity, MRI liver fat distribution and liver biopsy, patients will receive either 10 mg/day of Ezetimibe or placebo. Patients will be monitored at regular intervals for symptoms of liver disease, side effects of Ezetimibe and serum biochemical and metabolic indices. At the end of 24-weeks, patients will have a repeat medical evaluation, liver MRI and liver biopsy. Pre and post treatment MRI-derived liver fat content, liver histology and insulin sensitivity will be compared. The primary end point of successful therapy will be improvement in hepatic steatosis measured by MRI. Secondary end points will be improvement in insulin sensitivity, liver histology and liver biochemistry.

NCT01766713 Non Alcoholic Steatohepatitis Drug: Ezetimibe
MeSH: Fatty Liver Non-alcoholic Fatty Liver Disease
HPO: Hepatic steatosis

7. Hemochromatosis as defined by presence of 3+ or 4+ stainable iron on liver biopsy and homozygosity for C282Y or compound heterozygosity for C282Y/H63D. --- C282Y ---

Primary Outcomes

Measure: Change in Liver Fat as Measured by MRI-PDFF

Time: 24 weeks

32 HEPFER-Evaluation of a New Phenotypic Biological Marker in Genetic Type 1 Hemochromatosis

HFE(High iron FE)-related hereditary hemochromatosis has a highly variable penetrance. No phenotypic or genetic markers can predict the disease. The Iron Reabsorption Index (IRI), recently described by our group, correspond to the daily reabsorbed iron for a subject whose iron stock is stable and less than 50 µg / L. The IRI is constant over time, reflecting the importance of the underlying functional deficit. Hepcidin / ferritin (H / F) ratio may be an independent and constant over time marker of disease stage.No data are available on the validated values of this ratio. The goal of this project is to determine the intra-individual variations of the H / F ratio over time during maintenance therapy and to assess the correlation with the IRI.

NCT01784939 Hereditary Hemochromatosis C282Y Homozygous
MeSH: Hemochromatosis

Inclusion Criteria: - Men, at least 18 years old - hereditary hemochromatosis C282Y homozygous diagnosed and followed in the service of Liver Diseases, University Hospital of Rennes - Maintenance therapy with phlebotomy for at least 1 year with stable iron stock on the basis of at least four previous plasma ferritin < 50μg / L, - Written, free and informed consent Exclusion Criteria: - Intercurrent illness unrelated to hemochromatosis causing cytolysis or inflammatory reaction. --- C282Y ---

- Person with a measure of legal protection (guardianship) Inclusion Criteria: - Men, at least 18 years old - hereditary hemochromatosis C282Y homozygous diagnosed and followed in the service of Liver Diseases, University Hospital of Rennes - Maintenance therapy with phlebotomy for at least 1 year with stable iron stock on the basis of at least four previous plasma ferritin < 50μg / L, - Written, free and informed consent Exclusion Criteria: - Intercurrent illness unrelated to hemochromatosis causing cytolysis or inflammatory reaction. --- C282Y ---

- Person with a measure of legal protection (guardianship) Hereditary Hemochromatosis C282Y Homozygous Hemochromatosis HFE-related hereditary hemochromatosis has a highly variable penetrance : 1% of homozygous women and 30% of homozygous men would develop a clinically expressed disease. --- C282Y ---

The study involve 30 C282Y homozygous men, followed in a reference center with phlebotomy maintenance therapy and stabilized at a low level of ferritin (<50 µg / L) for at least 1 year. --- C282Y ---

Primary Outcomes

Description: values of Hepcidin / ferritin plasma ratio

Measure: distribution of values of Hepcidin / ferritin plasma ratio

Time: First dosage on an empty stomach at current time of phlebotomy (Day 0), second dosage at day 14 at the same time, third dosage at day 28 at the same time, fourth dosage at day 42 at the same time, fifth dosage at day 56 at the same time

Secondary Outcomes

Measure: Correlation between Hepcidin / ferritin plasma ratio and IRI.

Time: First dosage on an empty stomach at current time of phlebotomy (Day 0), second dosage at day 14 at the same time, third dosage at day 28 at the same time, fourth dosage at day 42 at the same time, fifth dosage at day 56 at the same time

Measure: Correlation between Hepcidin / Ferritin ratio before and after treatment

Time: First dosage on an empty stomach at current time of phlebotomy (Day 0), second dosage at day 14 at the same time, third dosage at day 28 at the same time, fourth dosage at day 42 at the same time, fifth dosage at day 56 at the same time

Measure: Distribution of inter-individual Hepcidin / Ferritin ratio according to the stage of liver fibrosis

Time: First dosage on an empty stomach at current time of phlebotomy (Day 0), second dosage at day 14 at the same time, third dosage at day 28 at the same time, fourth dosage at day 42 at the same time, fifth dosage at day 56 at the same time

33 Impact of Bloodletting on Iron Metabolism in Type 1 Hemochromatosis: Pathophysiological and Clinical Implications. Pilot Study.

Hemochromatosis type 1 is one of the most frequent genetic disease since the genetic predisposition (homozygosity for the C282Y mutation of the HFE gene) is encountered in about 3/1000 white subjects (5/1000 in Brittany, France). For the half of these predisposed subjects, the phenotypic expression of the disease needs a treatment. This treatment is based upon repeated bloodletting which is generally considered as simple, safe and effective. Nevertheless, it is still questioned as regard its physiopathological justification and its clinical implications. Indeed, bloodletting could cause an increase of non-transferrin bound iron (NTBI) particularly for its reactive form called labile plasma iron (LPI) This adverse physiopathological effect could have clinical consequences and could be linked with articular consequences which can be aggravated by the treatment.

NCT01810965 Hemochromatosis Type 1 Procedure: First evaluation phase : no intervention / Second evaluation phase: bloodletting of 7 ml/kg (with a maximum of 500ml)
MeSH: Hemochromatosis

Pilot Study.. Impact of Bloodletting on Iron Metabolism in Type 1 Hemochromatosis Hemochromatosis type 1 is one of the most frequent genetic disease since the genetic predisposition (homozygosity for the C282Y mutation of the HFE gene) is encountered in about 3/1000 white subjects (5/1000 in Brittany, France). --- C282Y ---

Inclusion Criteria: - Men - Age 18 years or older - Homozygosity for the C282Y mutation of the HFE gene - With an indication of treatment by bloodletting (in accordance with the French HAS guidelines) - Ferritinemia ≥ 500µg/L - Transferrin saturation ≥ 75% - Never treated by bloodletting - Written informed consent Exclusion Criteria: - Contraindication to bloodletting - Chronic inflammatory or dysmetabolic or neoplastic disease - Major cardiovascular disease - Excessive consumption of alcohol (≥ 3gr/day) - Treatment by iron chelators, C or E vitamins - Stay in altitude> 1500m in the month preceding the period Day 1 - Patients under guardianship - Blood donation in the 3 past months - Night / shift workers Inclusion Criteria: - Men - Age 18 years or older - Homozygosity for the C282Y mutation of the HFE gene - With an indication of treatment by bloodletting (in accordance with the French HAS guidelines) - Ferritinemia ≥ 500µg/L - Transferrin saturation ≥ 75% - Never treated by bloodletting - Written informed consent Exclusion Criteria: - Contraindication to bloodletting - Chronic inflammatory or dysmetabolic or neoplastic disease - Major cardiovascular disease - Excessive consumption of alcohol (≥ 3gr/day) - Treatment by iron chelators, C or E vitamins - Stay in altitude> 1500m in the month preceding the period Day 1 - Patients under guardianship - Blood donation in the 3 past months - Night / shift workers Hemochromatosis Type 1 Hemochromatosis Hemochromatosis type 1 is one of the most frequent genetic disease since the genetic predisposition (homozygosity for the C282Y mutation of the HFE gene) is encountered in about 3/1000 white subjects (5/1000 in Brittany, France). --- C282Y ---

Inclusion Criteria: - Men - Age 18 years or older - Homozygosity for the C282Y mutation of the HFE gene - With an indication of treatment by bloodletting (in accordance with the French HAS guidelines) - Ferritinemia ≥ 500µg/L - Transferrin saturation ≥ 75% - Never treated by bloodletting - Written informed consent Exclusion Criteria: - Contraindication to bloodletting - Chronic inflammatory or dysmetabolic or neoplastic disease - Major cardiovascular disease - Excessive consumption of alcohol (≥ 3gr/day) - Treatment by iron chelators, C or E vitamins - Stay in altitude> 1500m in the month preceding the period Day 1 - Patients under guardianship - Blood donation in the 3 past months - Night / shift workers Inclusion Criteria: - Men - Age 18 years or older - Homozygosity for the C282Y mutation of the HFE gene - With an indication of treatment by bloodletting (in accordance with the French HAS guidelines) - Ferritinemia ≥ 500µg/L - Transferrin saturation ≥ 75% - Never treated by bloodletting - Written informed consent Exclusion Criteria: - Contraindication to bloodletting - Chronic inflammatory or dysmetabolic or neoplastic disease - Major cardiovascular disease - Excessive consumption of alcohol (≥ 3gr/day) - Treatment by iron chelators, C or E vitamins - Stay in altitude> 1500m in the month preceding the period Day 1 - Patients under guardianship - Blood donation in the 3 past months - Night / shift workers Hemochromatosis Type 1 Hemochromatosis Hemochromatosis type 1 is one of the most frequent genetic disease since the genetic predisposition (homozygosity for the C282Y mutation of the HFE gene) is encountered in about 3/1000 white subjects (5/1000 in Brittany, France). --- C282Y --- --- C282Y ---

Inclusion Criteria: - Men - Age 18 years or older - Homozygosity for the C282Y mutation of the HFE gene - With an indication of treatment by bloodletting (in accordance with the French HAS guidelines) - Ferritinemia ≥ 500µg/L - Transferrin saturation ≥ 75% - Never treated by bloodletting - Written informed consent Exclusion Criteria: - Contraindication to bloodletting - Chronic inflammatory or dysmetabolic or neoplastic disease - Major cardiovascular disease - Excessive consumption of alcohol (≥ 3gr/day) - Treatment by iron chelators, C or E vitamins - Stay in altitude> 1500m in the month preceding the period Day 1 - Patients under guardianship - Blood donation in the 3 past months - Night / shift workers Inclusion Criteria: - Men - Age 18 years or older - Homozygosity for the C282Y mutation of the HFE gene - With an indication of treatment by bloodletting (in accordance with the French HAS guidelines) - Ferritinemia ≥ 500µg/L - Transferrin saturation ≥ 75% - Never treated by bloodletting - Written informed consent Exclusion Criteria: - Contraindication to bloodletting - Chronic inflammatory or dysmetabolic or neoplastic disease - Major cardiovascular disease - Excessive consumption of alcohol (≥ 3gr/day) - Treatment by iron chelators, C or E vitamins - Stay in altitude> 1500m in the month preceding the period Day 1 - Patients under guardianship - Blood donation in the 3 past months - Night / shift workers Hemochromatosis Type 1 Hemochromatosis Hemochromatosis type 1 is one of the most frequent genetic disease since the genetic predisposition (homozygosity for the C282Y mutation of the HFE gene) is encountered in about 3/1000 white subjects (5/1000 in Brittany, France). --- C282Y --- --- C282Y --- --- C282Y ---

Primary Outcomes

Measure: Maximal variation (delta maximum) of NTBI during the 5 days following a bloodletting

Time: Day 5

Secondary Outcomes

Measure: Kinetic of NTBI plasmatic concentration during the 5 days following a bloodletting

Time: Day 5

Measure: Maximal variation (delta maximum) of LPI during the 5 days following a bloodletting

Time: Day 5

Measure: Maximal variation (delta maximum) of hepcidin during the 5 days following a bloodletting

Time: Day 5

Measure: Kinetic of LPI plasmatic concentration during the 5 days following a bloodletting

Time: Day 5

Measure: Kinetic of hepcidin plasmatic concentration during the 5 days following a bloodletting

Time: Day 5

Measure: CRP

Time: Day 9, day 10, day 11 and day 12

Measure: Hemoglobin

Time: Day 9, day 10, day 11 and day 12

Measure: Soluble transferrin receptor

Time: Day 9, day 10, day 11 and day 12

Measure: EPO

Time: Day 9, day 10, day 11 and day 12

Measure: Circadian kinetic of NTBI plasmatic concentration when no bloodletting is performed

Time: Day 1

Measure: Circadian kinetic of API plasmatic concentration when no bloodletting is performed

Time: Day 1

Measure: Circadian kinetic of hepcidine plasmatic concentration when no bloodletting is performed

Time: Day 1

Measure: Maximal variation (delta maximum) of transferrin saturation during the 5 days following a bloodletting

Time: Day 5

Measure: Kinetic of transferrin saturation during the 5 days following a bloodletting

Time: Day 5

34 Deferasirox Versus Venesection in Patients With Hemochromatosis and for Treatment of Transfusional Siderosis in Myelodysplastic Syndrome: Diagnostics and New Biomarkers.

Hypothesis: Deferasirox can be used as a therapeutic agent to deplete the liver, heart and bone marrow of excess iron in patients with iron overload caused by myelodysplastic syndrome (MDS) and hemochromatosis (HC. Assess the effect of new serum biomarkers (NTBI and hepcidin) and MRI as indicators of iron overload and their usefulness to monitor iron depletion treatment. Study the effect of iron overload and iron depletion on intracellular signal transduction, trace metals concentrations in serum and urine and markers of oxidative stress in blood cells and urine.

NCT01892644 Hemochromatosis Myelodysplastic Syndromes Drug: Deferasirox Other: Venesection Drug: Deferasirox
MeSH: Preleukemia Myelodyspla Myelodysplastic Syndromes Hemochromatosis Iron Overload Syndrome
HPO: Myelodysplasia

Inclusion Criteria: - Patients with hemochromatosis, aged > 30 years, C282Y- homozygote, with serum-ferritin =/> 1000 µg/L - Patients aged > 18 years with verified low-risk or intermediate-1 risk of myelodysplastic syndrome, with normal cytogenetics and serum-ferritin > 1500 µg/L, or with a transfusion history of =/> red- blood-cell-transfusions. Exclusion Criteria: - Previous or current venesection - MDS patients eligible for hematopoietic stem cell transplantation - Subject complies with one or more of the following standard exclusion criteria for MRI examination; - If the patient has a pacemaker. --- C282Y ---

The most common are the classic C282Y and H63D point mutations of the hemochromatosis protein HFE, which disturbs its interaction with the transferrin receptor 1, the first step in the hepcidin signal cascade. --- C282Y ---

Homozygosity for C282Y is the strongest risk factor for serious iron overload and disease which develops after a long-lasting, asymptomatic period. --- C282Y ---

The study by Phatak et al (2010) was the first clinical trial to demonstrate the safety and efficacy of deferasirox in patients with C282Y-homzygot hemochromatosis. --- C282Y ---

Primary Outcomes

Measure: Changes from baseline in liver iron concentration (LIC) and heart iron concentration (HIC) determined by Magnetic Resonance Imaging (MRI), and in bone marrow iron content determined by microscopy after treatment with deferasirox.

Time: 0, 6 and 12 months

Secondary Outcomes

Measure: Change of hepcidin concentration in serum

Time: 0, 6 and 12 months

Measure: Change of non-transferrin bound iron (NTBI) concentration in serum

Time: 0, 6 and 12 months

Measure: Change of multiple trace metals in serum

Time: 0, 6 and 12 months

Measure: Change of intracellular signal molecules, mTOR, NFkB and stress sensor p53 in blood cells

Time: 0, 6 and 12 months

Description: Marker of oxidative DNA damage

Measure: Change of 8-oxodG in urine

Time: 0, 6 and 12 months

Description: Cu,Zn-Super Oxid Dismutase (SOD)is an antioxidant enzyme

Measure: Change of Cu,Zn-SOD activity in erythrocyte hemolysate

Time: 0, 6 and 12 months

Description: Serum analysis

Measure: Clinical chemistry: Na, K, Ca, Creatinine, creatinine kinase, CRP, alanine aminotransferase (ALAT), aspartate aminotransferase (ASAT), alkaline phosphatase (ALP), gamma-glutamyl transferase (GT), lactate dehydrogenase (LD), albumin, bilirubin.

Time: 0, 2,4,6,8 weeks, 3,4,5,6,7,8,9,10,11,12 months, 5 weeks posttreatment

Description: Morning spot urine sample.

Measure: Urine routine test strip for detection of blood, protein, and nitrite

Time: 0,2,4,6,8 weeks and 3,4,5,6,7,8,9,10,11,12 months

Measure: Ferritin concentration in serum

Time: 0,2,4,6,8 weeks, 3,4,5,6,7,8,9,10,11,12 months, 5 weeks post treatment

Measure: Transferrin saturation in serum

Time: 0,2,4,6,8 weeks, 3,4,5,6,7,8,9,10,11,12 months, 5 weeks post treatment

Measure: HbA1c

Time: 0, 2,6,12 months

Measure: INR ( International normalized ratio)

Time: 0,2,6,12 months

Measure: Analysis of hemoglobin, reticulocytes, hematocrit, MCV, leukocyte count (total and differential), and platelets

Time: 0, 2,4,6,8 weeks, 3,4,5,6,7,8,9,10,11,12 months, 5 weeks posttreatment

Measure: Urine trace metals

Time: 0, 6 and 12 months

Measure: Bone marrow sample

Time: 0, 6 and 12 months

Other Outcomes

Measure: Pregnancy urin test (hCG)

Time: 0, 6 and 12 months, 5 weeks posttreatment

35 Sitagliptin Versus Placebo in the Treatment of Non-alcoholic Fatty Liver Disease

Nonalcoholic fatty liver disease (NAFLD) represents a spectrum of diseases ranging from simple steatosis to nonalcoholic steatohepatitis (NASH), the progressive form of liver disease that can lead to cirrhosis and liver-related mortality in persons who drink little or no alcohol. NAFLD is defined as the presence of hepatic steatosis with no evidence of hepatocellular injury in the form of ballooning of the hepatocytes. NASH is defined as the presence of hepatic steatosis and inflammation with hepatocyte injury (ballooning) with or without fibrosis. NASH is benign in many affected individuals but can cause progressive liver injury and, indeed, may be the major cause of cryptogenic cirrhosis1. Currently, there is no FDA approved treatment for NAFLD. Weight loss and exercise are the recommended but often difficult maintain these lifestyle changes in the long term and therefore therapeutic agents have been investigated. In this study, we propose to treat 50 patients with NAFLD and diabetes with either sitagliptin or placebo for 24 weeks. After an initial evaluation for insulin sensitivity and MRI liver fat distribution, patients will receive either 100 mg/day of sitagliptin or placebo. Patients will be monitored at regular intervals for symptoms of liver disease, side effects of sitagliptin and serum biochemical and metabolic indices. At the end of 24-weeks, patients will have a repeat medical evaluation, liver MRI and an optional liver biopsy. Pre and post treatment MRI-derived liver fat content and insulin sensitivity will be compared. The primary end point of successful therapy will be improvement in hepatic steatosis measured by MRI. Secondary end points will be improvement in insulin sensitivity and liver biochemistry.

NCT01963845 Non-alcoholic Fatty Liver Disease Drug: Sitagliptin Drug: Placebo
MeSH: Liver Diseases Fatty Liver Non-alcoholic Fatty Liver Disease
HPO: Abnormality of the liver Decreased liver function Elevated hepatic transaminase Hepatic steatosis

- Hemochromatosis as defined by presence of 3+ or 4+ stainable iron on liver biopsy and homozygosity for C282Y or compound heterozygosity for C282Y/H63D. --- C282Y ---

Primary Outcomes

Description: Participants liver fat was measured at baseline and 24 weeks. This is the percentage change in liver fat assessed by MRI-PDFF and stratified by treatment group.

Measure: Percentage Change in Liver Fat Relative to Baseline Assessed by MRI-PDFF

Time: Baseline and 24 weeks

Secondary Outcomes

Description: AST, measured in IU/L at baseline and 24 weeks

Measure: AST, Aspartate Aminotransferase

Time: Baseline and 24 weeks

Description: ALT, measured in IU/L at baseline and 24 weeks

Measure: ALT, Alanine Aminotransferase

Time: Baseline and 24 weeks

Description: LDL, measured in mg/dL at baseline and 24 weeks

Measure: LDL, Low-density Lipoprotein

Time: Baseline and 24 weeks

Description: HOMA-IR, calculated as [(glucose (mg/dL) X insulin (mg/dL)) / 405 ] at baseline and 24 weeks

Measure: HOMA-IR, Homeostatic Model Assessment of Insulin Resistance

Time: Baseline and 24 weeks

36 Treatment of Refractory Hemochromatosis Rheumatism by Anakinra: a Preliminary Phase II Study

Treatment of refractory hemochromatosis rheumatism by Anakinra. Prospective, multicenter, non-randomised, single-arm, open-label, phase II trial.

NCT02263638 Refractory Hemochromatosis Rheumatism Drug: Anakinra
MeSH: Rheumatic Diseases Hemochromatosis Collagen Diseases

Inclusion Criteria: - Patients with age equal to or over 18 years old, - Patients with proved hereditary hemochromatosis with homozygosity for the C282Y mutation of the HFE gene, - Patients with rheumatism related to hemochromatosis, considered by the rheumatologist refractory to usual treatment defined by a persistent painful symptomatology despite a treatment of at least one month with level 2 analgesics (weak opioids) at maximal dose, NSAID, colchicine, steroid injection or a combination of these treatments, - Patients with pain > 40/100mm measured by VAS (pain of the last 48 hours), - Effective contraception to be used during treatment and until 48h after the last administration for women of reproductive age, - Patients who have given written informed consent. --- C282Y ---

Primary Outcomes

Description: Improvement is defined as the minimal clinically important improvement of joint pain and is assessed on a 0-100 mm visual analogue scale (VAS)

Measure: Rate of patients with improvement of joint pain

Time: Day 15

Secondary Outcomes

Description: Assessment of the disease activity by Visual analog scale (VAS)

Measure: Assessment of the disease activity

Time: Day 0, day 15, day 30, day 60, day 90

Description: Assessment of the number of painful joints by a clinical exam

Measure: Assessment of the number of painful joints

Time: Day 0, day 15, day 30, day 60, day 90

Description: Assessment of the number of swollen joints by a clinical exam

Measure: Assessment of the number of swollen joints

Time: Day 0, day 15, day 30, day 60, day 90

Measure: Assessment of analgesics consumption

Time: Day 0, day 15, day 30, day 60, day 90

Measure: Assessment of non-steroidal anti-inflammatory drugs (NSAID) consumption

Time: Day 0, day 15, day 30, day 60, day 90

Measure: Assessment of colchicine consumption

Time: Day 0, day 15, day 30, day 60, day 90

Measure: Assessment of steroids injections consumption

Time: Day 0, day 15, day 30, day 60, day 90

Description: Assessment of the quality of life by the SF36 questionnaire

Measure: Assessment of the quality of life

Time: Day 0, day 15, day 30, day 90

Description: Assessment of the quality of life by the HAQ questionnaire

Measure: Assessment of the quality of life

Time: Day 0, day 15, day 30, day 90

Description: Functional evaluation by WOMAC index for hip and knee

Measure: Functional evaluation

Time: Day 0, day 15, day 30, day 90

Description: Functional evaluation by Dreiser index for hands

Measure: Functional evaluation

Time: Day 0, day 15, day 30, day 90

Description: Assessment of joint damage by X-rays and Doppler ultrasound

Measure: Assessment of joint damage

Time: Day 0, day 90

Description: Puncture if acute joint effusion : cells count

Measure: Synovial fluid analysis

Time: 3 months

Description: Puncture if acute joint effusion : search for crystals presence

Measure: Synovial fluid analysis

Time: 3 months

Description: Puncture if acute joint effusion : iron parameters markers

Measure: Synovial fluid analysis

Time: 3 months

Description: Biological/Vaccine : iron and inflammatory markers

Measure: Biological effects on inflammation and iron metabolism

Time: Day 0, day 15, day 30, day 60, day 90

Description: Pharmacokinetics study

Measure: Time at which Cmax of anakinra was observed (Tmax)

Time: Predose, 0.25, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 10, 12, 15, 18, 21, 24 hours post-dose

Description: Pharmacokinetics study

Measure: Maximum observed concentration (Cmax) of anakinra

Time: Predose, 0.25, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 10, 12, 15, 18, 21, 24 hours post-dose

Description: Pharmacokinetics study

Measure: Half-life (T1/2) of anakinra

Time: Predose, 0.25, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 10, 12, 15, 18, 21, 24 hours post-dose

Description: Pharmacokinetics study

Measure: Area under the concentration-time curve of time 0 to the last detectable concentration (AUC0−last) of anakinra

Time: Predose, 0.25, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 10, 12, 15, 18, 21, 24 hours post-dose

Description: Pharmacokinetics study

Measure: Area under the concentration-time curve of time 0 to infinity (AUC0−∞) of anakinra

Time: Predose, 0.25, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 10, 12, 15, 18, 21, 24 hours post-dose

Description: Pharmacokinetics study

Measure: Plasma clearance after administration (CL/F) of anakinra

Time: Predose, 0.25, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 10, 12, 15, 18, 21, 24 hours post-dose

37 Natural History of Noncirrhotic Portal Hypertension

Background: - Noncirrhotic Portal Hypertension (NCPH) is caused by liver diseases that increase pressure in the blood vessels of the liver. It seems to start slowly and not have many warning signs. Many people may not even know that they have a liver disease. There are no specific treatments for NCPH. Objectives: - To learn more about how NCPH develops over time. Eligibility: - People age 12 and older who have NCPH or are at risk for getting it. In the past year, they cannot have had other types of liver disease that typically result in cirrhosis, liver cancer, or active substance abuse. Design: - Participants will have 2 screening visits. - Visit 1: to see if they have or may develop NCPH. - Medical history - Physical exam - Urine and stool studies - Abdominal ultrasound - Fibroscan. Sound waves measure liver stiffness. - Visit 2: - Blood tests - Abdominal MRI - Echocardiogram - Questionnaire - Liver blood vessel pressure (hepatic venous portal gradient (HVPG)) measurement. This is done with a small tube inserted in a neck vein. - They may have a liver biopsy. - All participants will visit the clinic every 6 months for a history, physical exam, and blood tests. They will also repeat some of the screening tests yearly. - Participants with NCPH will also have: - Upper endoscopy test. A tube inserted in the mouth goes through the esophagus and stomach. - At least every 2 years: Esophagogastroduodenoscopy. - At least every 4 years: testing including HVPG measurements and liver biopsy. - Participants without NCPH will also have: - Liver biopsy and HVPG measurements to see if they have NCPH. - Every 2 years: abdominal MRI and stool studies. - The study will last indefinitely.

NCT02417740 Cystic Fibrosis Immunologic Deficiency Syndrome Turner Syndrome Congenital Hepatic Fibrosis Idiopathic Non-Cirrhotic Portal Hypertension
MeSH: Cystic Fibrosis Hypertension, Hypertension, Portal Turner Syndrome Hypertension Immunologic Deficiency Syndromes Syndrome Fibrosis
HPO: Hypertension Immunodeficiency Portal hypertension

- Hemochromatosis as defined by presence of 3+ or 4+ stainable iron on liver biopsy or homozygosity for C282Y. --- C282Y ---

Primary Outcomes

Description: natural history study

Measure: To study the natural history of non cirrhotic portal hypertension. It is an ongoing study

Time: Ongoing

38 Hepcicor Cohort : Clinical, Biological, Genetic and Fonctional charactérization of Rare Iron Overlaod phénotypes Associated With Hepcidin Deficiency Excluding C282Y Homozygosity

The study explores the hepcidin deficiency causes of rare iron overload (excluding C282Y homozygosity), and aim to characterize this iron overload in term of clinical, biological, genetic and functional spacificities.

NCT02619955 Rare Iron Overlaods Other: samples with DNA

Hepcicor Cohort : Clinical, Biological, Genetic and Fonctional charactérization of Rare Iron Overlaod phénotypes Associated With Hepcidin Deficiency Excluding C282Y Homozygosity. --- C282Y ---

Cohort of Patients With Rare Iron Overloads Excluding C282Y Homozygosity The study explores the hepcidin deficiency causes of rare iron overload (excluding C282Y homozygosity), and aim to characterize this iron overload in term of clinical, biological, genetic and functional spacificities. --- C282Y ---

Cohort of Patients With Rare Iron Overloads Excluding C282Y Homozygosity The study explores the hepcidin deficiency causes of rare iron overload (excluding C282Y homozygosity), and aim to characterize this iron overload in term of clinical, biological, genetic and functional spacificities. --- C282Y --- --- C282Y ---

to characterize these iron overloads with phenotype of hepcidin deficiency not related to homozygosity C282Y (clinical, biological and genetic).. comparison of the hepcidin and hepcidin/ferritin ratio in patient with or without in gene known to be associated with iron metabolism. --- C282Y ---

Exclusion Criteria: - HFE hemochromatosis: homozygosity C282Y/C282Y - Treatment with iterative phlebotomy - Hematologic diseases with dyserythropoiesis and/or repeated transfusions - Haptoglobin low, below normal directing towards the diagnosis of chronic hemolysis, myelodysplasia - Prolonged oral or parenteral iron supplementation - Current or past excessive regular drinking - Patient minor or under legal protection measure Inclusion Criteria: - Biological profile suggestive of hepcidin deficiency: - increase of transferrin saturation coefficient (> 50 %) verified on at least 2 times, and calculated from the transferrinemia. --- C282Y ---

Exclusion Criteria: - HFE hemochromatosis: homozygosity C282Y/C282Y - Treatment with iterative phlebotomy - Hematologic diseases with dyserythropoiesis and/or repeated transfusions - Haptoglobin low, below normal directing towards the diagnosis of chronic hemolysis, myelodysplasia - Prolonged oral or parenteral iron supplementation - Current or past excessive regular drinking - Patient minor or under legal protection measure Rare Iron Overlaods Chronic iron overload are responsible for morbidity and mortality. --- C282Y ---

The main objective of this study is to characterize these iron overloads with phenotype of hepcidin deficiency not related to homozygosity C282Y (clinical, biological and genetic). --- C282Y ---

Primary Outcomes

Description: to characterize these iron overloads with phenotype of hepcidin deficiency not related to homozygosity C282Y (clinical, biological and genetic).

Measure: Number of patients presenting with mutation in gene know to be associated with iron metabolism

Time: Inclusion

Secondary Outcomes

Description: To Identificate potential explanatory factors of hepcidino deficiency phenotype

Measure: comparison of the hepcidin and hepcidin/ferritin ratio in patient with or without in gene known to be associated with iron metabolism

Time: inclusion

Description: - Identification of potentially explanatory factors visceral consequences of iron overload in hepcidino deficiency phenotype (overweight, high blood pressure, diabetes)

Measure: Number of patients presenting with associated causes of iron overload

Time: inclusion

Description: To Research correlations genotype-phenotype

Measure: Genotype-Phenotype correlation

Time: Inclusion

Description: Validation of the hepatic iron concentration measurements imaging ( nuclear magnetic resonance (NMR)) in the various centers

Measure: Hepatic and splenic iron concentration measurements by NMR

Time: Inclusion

Description: - Assessment of the clinical value of biomarkers of iron metabolism

Measure: Number of patients with detectable abnormal iron species in blood (non transferrin bound iron, labile pool iron)

Time: Inclusion

39 Aramchol Versus Placebo in the Treatment of HIV-associated Nonalcoholic Fatty Liver Disease and Lipodystrophy: A Randomized, Double-blinded, Allocation-concealed, Placebo-controlled Clinical Trial

A subset of patients with NAFLD that have not been extensively studied are those infected with human immunodeficiency virus (HIV). Currently, there is no FDA approved treatment for NAFLD or NASH. Additionally, there have been no significant clinical trials for HIV patients with NAFLD and there are no approved treatment options. We plan to conduct a randomized, double-blinded, placebo-controlled clinical trial to examine the efficacy of 600 mg of Aramchol daily (including 200 mg tablet and 400 mg tablet) versus identical placebo given over 12 weeks to improve HIV-associated hepatic steatosis as measured by a validated and accurate magnetic resonance imaging (MRI)-based technique.

NCT02684591 Nonalcoholic Fatty Liver Disease HIV Drug: Aramchol Drug: Placebo
MeSH: Liver Diseases Fatty Liver Non-alcoholic Fatty Liver Disease Lipodystrophy
HPO: Abnormality of the liver Decreased liver function Elevated hepatic transaminase Hepatic steatosis Lipodystrophy

Evidence of another form of liver disease: Hepatitis B as defined as presence of hepatitis B surface antigen (HBsAg), Hepatitis C as defined by presence of hepatitis C virus (HCV) RNA in serum, Autoimmune hepatitis as defined by anti-nuclear antibody (ANA) of 1:160 or greater and liver histology consistent with autoimmune hepatitis or previous response to immunosuppressive therapy, Autoimmune cholestatic liver disorders as defined by elevation of alkaline phosphatase and anti-mitochondrial antibody of greater than 1:80 or liver histology consistent with rimary biliary cirrhosis or elevation of alkaline phosphatase and liver histology consistent with sclerosing cholangitis, Wilsons disease as defined by ceruloplasmin below the limits of normal and liver histology consistent with Wilsons disease Alpha-1-antitrypsin deficiency as defined by alpha-1-antitrypsin level less than normal and liver histology consistent with alpha-1-antitrypsin deficiency hemochromatosis as defined by presence of 3+ or 4+ stainable iron on liver biopsy and homozygosity for C282Y or compound heterozygosity for C282Y/H63D, Drug-induced liver disease as defined on the basis of typical exposure and history,Bile duct obstruction as shown by imaging studies. --- C282Y ---

Primary Outcomes

Description: To examine the efficacy of aramchol at 600 mg orally daily versus placebo in improving hepatic steatosis assessed by magnetic resonance imaging in patients with HIV-associated NAFLD

Measure: Efficacy of Aramchol 600 mg vs. Placebo in Improving Hepatic Steatosis Assessed by Magnetic Resonance Imaging in Patients With HIV-associated NAFLD

Time: 12 weeks

Secondary Outcomes

Description: To examine the efficacy of two doses of aramchol: 200 mg/tablet and 400 mg/tablet / day orally daily versus placebo in improving serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels in patients with HIV-associated NAFLD

Measure: Efficacy of Aramchol 600 mg Orally Daily Versus Placebo in Improving Serum Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) Levels in Patients With HIV-associated NAFLD

Time: 12 Weeks

Other Outcomes

Description: To examine the efficacy of aramchol in improving imaging-based biomarkers associated with changes in NAFLD

Measure: Efficacy of Aramchol in Improving Imaging-based Biomarkers Associated With Changes in NAFLD

Time: 12 weeks

40 Iron Supplement Effect Over Immune System and Neurobehavioral Child Development.

Objective: To evaluate the effect of Iron supplement with two different amounts (one in the higher limit and another in the lower limit of the suggested amount) according to the presence of mutations in the HFE gene in the physical, immune and neurobehavioral development in the 6 to 12 moth toddlers. Methodology: Subjects: 340 toddlers coming from Paediatric Serves of Sant Joan Hospital. Methods: At 6 and 12 months it done clinical history, food registry, biochemist determinations: haemoglobin, iron, transferrin, ferritin, reactive C protein and immune response (IL4, IL10, IL6 IFN, IgA, IgM, IgG, IgE). Mutations in the HFE gene: C282Y, H63D, S65D and hepcidin gene. Mental, psychomotor and behavioual development (Bayley Scales of Infant Development 2on Edition: 1993). We evaluate the level of language and communication (MacArthur), regulation and sensory process (Infant Toddler Symptom Checklist), familiar and environment surroundings (Scale Health General Parental Stress Index).

NCT02690675 Neurodevelopmental Disorders Lactation Dietary Supplement: Iron fortified formula milk
MeSH: Neurodevelopmental Disorders

Mutations in the HFE gene: C282Y, H63D, S65D and hepcidin gene. --- C282Y ---

Primary Outcomes

Measure: Mental and psychomotor development with BSID (Bayley Scale of Infant Development) at 12 months.

Time: 12 months

Secondary Outcomes

Measure: Height at 12 months measured in centimeters

Time: 12 months

Measure: Weight at 12 months measured in grams

Time: 12 months

Measure: Head circumference at 12 months measured in centimeters

Time: 12 months

Measure: Risk of infections at 12 months measured qualitatively from record of presence or not of various infections as bronchitis, rhinitis, otitis etc.

Time: 12 months

41 A Phase 2,Multicenter,Open-Label Study to Investigate the Efficacy, Safety and Pharmacokinetics of Ritonavir-boosted Danoprevir in Combination With Peg-IFN and RBV in Treatment-Naive Non-Cirrhotic Patients Who Have Chronic Hepatitis GT1

The purpose of this study is to evaluate the Efficacy, Safety and Pharmacokinetics of Ritonavir-boosted Danoprevir (ASC08) in Combination with Peg-IFN and RBV in Treatment-Naive Non-Cirrhotic Patients Who Have Chronic Hepatitis Genotype 1.

NCT03020004 Chronic Hepatitis C Drug: Danoprevir Drug: Ritonavir Drug: peginterferon alfa-2a Drug: Ribavirin (RBV)
MeSH: Hepatitis C Hepatitis C, Chronic Hepatitis Hepatitis, Chronic
HPO: Chronic active hepatitis Chronic hepatitis Hepatitis

Patients who have not obtained a liver biopsy or Fibroscan in the last 1 years will have a study related Fibroscan performed in order to confirm the diagnosis - Others as specified in the detailed protocol Exclusion Criteria: - Patients with Fibroscan detection value > 12.9 kPa, or histologic examination for liver cirrhosis patients - Presence or history of non-hepatitis C chronic liver disease, including but not limited to, autoimmune hepatitis, α-1-antitrypsin deficiency, C282Y homozygous hemochromatosis, Wilson's disease, drug- or toxin-induced liver disease, alcohol-related liver disease, primary biliary cirrhosis, sclerosing cholangitis, and porphyria cutanea tarda causing liver pathology or requiring phlebotomy - Patients with a history of liver cell cancer, screening before or screening suspected hepatocellular carcinoma (HCC) patients, or imaging studies found suspicious nodules, or AFP > 50 ng/mL - Positive hepatitis A antibody,positive hepatitis B surface antigen,syphilis antibody or HIV antibody at screening - Others as specified in the detailed protocol Inclusion Criteria: - Willing and able to provide written informed consent - Chronic HCV infection (≥ 6 months) ; - Positive HCV antibody - Serum HCV RNA of ≥ 1 × 104 IU/mL - Hepatitis C virus GT1 - Never received prior-treatment for HCV with interferon, RBV, or other direct-acting or host-targeting antivirals for HCV - The liver biopsy methods in the protocol (non-cirrhosis is defined as: Metavir score ˂ 4), or as determined by Fibroscan defined as: ˂ 14.6 kPa. --- C282Y ---

Patients who have not obtained a liver biopsy or Fibroscan in the last 1 years will have a study related Fibroscan performed in order to confirm the diagnosis - Others as specified in the detailed protocol Exclusion Criteria: - Patients with Fibroscan detection value > 12.9 kPa, or histologic examination for liver cirrhosis patients - Presence or history of non-hepatitis C chronic liver disease, including but not limited to, autoimmune hepatitis, α-1-antitrypsin deficiency, C282Y homozygous hemochromatosis, Wilson's disease, drug- or toxin-induced liver disease, alcohol-related liver disease, primary biliary cirrhosis, sclerosing cholangitis, and porphyria cutanea tarda causing liver pathology or requiring phlebotomy - Patients with a history of liver cell cancer, screening before or screening suspected hepatocellular carcinoma (HCC) patients, or imaging studies found suspicious nodules, or AFP > 50 ng/mL - Positive hepatitis A antibody,positive hepatitis B surface antigen,syphilis antibody or HIV antibody at screening - Others as specified in the detailed protocol Chronic Hepatitis C Hepatitis C Hepatitis C, Chronic Hepatitis Hepatitis, Chronic null --- C282Y ---

Primary Outcomes

Description: SVR12, defined as undetectable HCV RNA 12 weeks after the last day of study drug administration

Measure: Percentage of Subjects With Sustained Virologic Response (SVR12) 12 Weeks Post-treatment

Time: 24 weeks

42 Phase 2 Study To Investigate the Efficacy, Safety And Pharmacokinetics Of Ravidasvir In Combination With Ritonavir-boosted Danoprevir And Ribavirin In Treatment-naive Non-cirrhotic Taiwanese Patients Who Have Chronic Hepatitis C Genotype 1

The purpose of this study is to evaluate the efficacy, safety and tolerability of Ravidasvir (ASC16) in combination with Ritonavir-boosted Danoprevir(ASC08) and Ribavirin in treatment-naive no-cirrhotic Taiwanese patients who have chronic hepatitis C genotype1.

NCT03020095 Chronic Hepatitis C Drug: Ravidasvir Drug: Danoprevir Drug: Ritonavir Drug: Ribavirin
MeSH: Hepatitis C Hepatitis C, Chronic Hepatitis Hepatitis, Chronic
HPO: Chronic active hepatitis Chronic hepatitis Hepatitis

- History or presence of decompensated liver disease (history of ascites, hepatic encephalopathy, HCC, or bleeding esophageal varices) - Presence or history of non-hepatitis C chronic liver disease, including but not limited to, autoimmune hepatitis, α-1-antitrypsin deficiency, C282Y homozygous hemochromatosis, Wilson's disease, drug- or toxin-induced liver disease, alcohol-related liver disease, primary biliary cirrhosis, sclerosing cholangitis, and porphyria cutanea tarda causing liver pathology or requiring phlebotomy - Positive hepatitis B surface antigen or HIV antibody at screening - History or presence of liver cirrhosis - History of severe psychiatric disease, including psychosis and/or depression, who is not able to participate or able to give written informed consent and to comply with the study restrictions - History of active malignancy within the last 5 years, with the exception of localized or in situ carcinoma (e.g., basal or squamous cell carcinoma of the skin) - History of severe cardiac disease (e.g., New York Heart Association Functional Class III or IV, myocardial infarction within 6 months, ventricular tachyarrhythmia's requiring ongoing treatment, unstable angina or other unstable, uncontrolled or significant cardiovascular disease within 6 months). --- C282Y ---

Primary Outcomes

Description: SVR12, defined as undetectable HCV RNA 12 weeks after the last day of study drug administration

Measure: Proportion of participants with Sustained Virologic Response 12 weeks after end of treatment (SVR12)

Time: 12 weeks

Secondary Outcomes

Measure: Proportion of participants permanently discontinuing study drug(s) due to an adverse event (AE)

Time: 24 weeks

Description: SVR24, defined as undetectable HCV RNA 24 weeks after the last day of study drug administration

Measure: Proportion of participants with Sustained virologic response 24 weeks after end of treatment

Time: 24 weeks

43 Effectiveness of Adaptation of the Dose of Iron Supplementation in Pregnancy on Maternal-child Health. Randomized Clinical Trial (ECLIPSES)

Currently, there is no consensus regarding iron supplementation dose that is most beneficial for maternal and offspring health during gestation. This deficit, or excess, of iron prejudices the mother-child wellbeing. Therefore the hypotheses are that an iron supplementation adapted to values of hemoglobin at the start of the pregnancy will would be more effective in preventing iron deficiency, without increasing the risk of hemoconcentration by the end of pregnancy. This would be helped optimize mother-child health status. The aims of the study are to determine the highest level of effectiveness of iron supplementation adapted to hemoglobin (Hb) levels in early pregnancy, which would be optimum for mother-child health. To accomplish this objective a Randomized Clinical Trial (RCT) triple-blinded was designed. The study is structured as a RCT with 2 strata, depending on the Hb levels before week 12 of gestation. Stratum 1: If Hb from 110 to 130 g/L, randomly assigned at week 12 to receive iron supplement of 40 or 80 mg/d. Stratum 2: If Hb >130 g/L, randomly assigned at week 12 to receive iron supplement of 40 or 20 mg/d. This study will be conducted in non-anemic pregnant women at early gestation stage, and their subsequent newborns. The data recollected to mothers will be: socio-economic data, clinical history, food item frequency, lifestyle and emotional state, and adherence to iron supplement prescription. In addition, biochemical measured will be Hemoglobin, serum ferritin, C reactive protein, cortisol, and alterations in the HFE gene (C282Y, H63D). In children, the data collected will be: ultrasound fetal biometry, anthropometric measurements, and temperament development Should conclusive outcomes be reached, the study would indicate the optimal iron supplementation dose required to promote maternal and infant health. These results would contribute towards developing guidelines for good clinical practice.

NCT03196882 Anemia Ferropenic Risk of Hemoconcentration (Iron Levels Risk of Hemoconcentration (Iron Levels > Risk of Hemoconcentration (Iron Levels >130g/L) Drug: 40mg/day of iron Drug: 20mg/day of iron Drug: 80mg/day of iron
MeSH: Anemia Anemia, Iron-Deficiency
HPO: Anemia Iron deficiency anemia

In addition, biochemical measured will be Hemoglobin, serum ferritin, C reactive protein, cortisol, and alterations in the HFE gene (C282Y, H63D). --- C282Y ---

- Hemoconcentration risk is defined as: Hb >130 g/L in the 2nd and /or3rd trimester (Peña-Rosas y Viteri, 2009).. C282Y polymorphisms of HFE gene. --- C282Y ---

Presence or absence of polymorphisms: C282Y and H63D. --- C282Y ---

Primary Outcomes

Description: - Anemia is defined as Hb <110 g/L in the 1st and 3rd trimester, Hb <110 in 2nd trimester (Centers for Disease Control and Prevention, 1998).

Measure: Anemia

Time: at week 36 of gestation (3rd visit of study)

Description: - Ferropenic anemia is defined as: Hb < the normal limit, and serum ferritin (SF) <15 μg/L (WHO, 2007)

Measure: ferropenic anemia

Time: at week 36 of gestation (3rd visit of study)

Description: - Hemoconcentration risk is defined as: Hb >130 g/L in the 2nd and /or3rd trimester (Peña-Rosas y Viteri, 2009).

Measure: Risk of hemoconcentration

Time: at week 36 of gestation (3rd visit of study)

Secondary Outcomes

Description: Presence or absence of polymorphisms: C282Y and H63D

Measure: C282Y polymorphisms of HFE gene

Time: Blood analysis at 12 weeks of gestation.

Description: weight (g)

Measure: Anthropometric parameters of newborn.

Time: At birth

Description: Units on a scale (score).

Measure: Neurorconductual development of newborn (Bayley Scales)

Time: 40days post-partum

Description: Presence or absence of polymorphisms: C282Y and H63D

Measure: H63D polymorphisms of HFE gene

Time: Blood analysis at 12 weeks of gestation.

44 A Phase II, Multicenter, Open-label, Randomized Two-year Study to Evaluate the Efficacy and Safety of Deferasirox Film-coated Tablet Versus Phlebotomy in Patients With Hereditary Hemochromatosis.

The purpose of this study is to evaluate the efficacy and safety of deferasirox film coated tablet (FCT) versus phlebotomy for the management of iron overload in adults with HH at risk of iron-related morbidity. This evaluation will provide information on the two treatment options in terms of the rate of response of proportion of patients reaching the study target SF ≤ 100 μg/L and their associated safety profiles. In addition to exploring the safety and efficacy of deferasirox FCT in hereditary hemochromatosis (HH), this study is being conducted to fulfill an FDA post-marketing requirement [PMC 750-10 (Exjade) /PMR 2888-8 (Jadenu)] to provide additional randomized data to confirm the ocular safety profile of deferasirox through detailed ocular assessments in patients treated with deferasirox FCT for 2 years.

NCT03203850 Hereditary Hemochromatosis Drug: Deferasirox FCT Procedure: Phlebotomy
MeSH: Hemochromatosis

Male or female ≥ 18-years-old 2. Documented genotype testing confirming homozygous for the C282Y mutation (C282Y/C282Y) 3. Transferrin saturation ≥ 45% (at either screening visit) 4. Serum ferritin (SF) ≥ 500 μg/L (at either screening visit) - Exclusion Criteria: 1. Medical conditions that preclude inclusion: - Iron overload not due to HH - Condition which might significantly alter the absorption, distribution, metabolism or excretion of oral deferasirox - Systemic disease which prevents taking study treatment or any contraindication to phlebotomy - Inflammatory condition or immunological disease which may interfere with the SF interpretation, such as an active infection, collagen vascular disorders, irritable bowel syndrome, lupus, or immune thrombocytopenia - Significantly impaired gastrointestinal function or disease that may significantly alter the absorption of oral deferasirox, e.g. --- C282Y ---

Male or female ≥ 18-years-old 2. Documented genotype testing confirming homozygous for the C282Y mutation (C282Y/C282Y) 3. Transferrin saturation ≥ 45% (at either screening visit) 4. Serum ferritin (SF) ≥ 500 μg/L (at either screening visit) - Exclusion Criteria: 1. Medical conditions that preclude inclusion: - Iron overload not due to HH - Condition which might significantly alter the absorption, distribution, metabolism or excretion of oral deferasirox - Systemic disease which prevents taking study treatment or any contraindication to phlebotomy - Inflammatory condition or immunological disease which may interfere with the SF interpretation, such as an active infection, collagen vascular disorders, irritable bowel syndrome, lupus, or immune thrombocytopenia - Significantly impaired gastrointestinal function or disease that may significantly alter the absorption of oral deferasirox, e.g. --- C282Y --- --- C282Y ---

Primary Outcomes

Description: Assess the response rate (RR) of deferasirox film coated tablet (FCT) and phlebotomy treatment arms where response is defined by achieving target serum ferritin (SF) ≤ 100 μg/L on or before 24 months. Estimate of the RR and corresponding 95% confidence interval (CI) will be provided for each arm. No formal hypothesis testing is planned in this study.

Measure: Proportion of patients achieving target SF ≤ 100 μg/L for the first time.

Time: Response is defined by achieving target SF ≤ 100 μg/L on or before 24 months.

Secondary Outcomes

Description: To evaluate the ocular safety of deferasirox FCT and phlebotomy over 24 months. To characterize long-term ocular safety by the incidence of treatment-emergent ocular adverse events (AEs) (new or worsening from baseline) summarized categorically by system organ class and/or preferred term.

Measure: Incidence of ocular adverse events (AEs) overall

Time: 24 months

Description: To evaluate the ocular safety of deferasirox FCT and phlebotomy over 24 months. To characterize long-term ocular safety by AE severity (new or worsening from baseline) summarized categorically by system organ class and/or preferred term.

Measure: Incidence of ocular adverse events (AEs) by severity

Time: 24 months

45 Prospective Cohort Assessing the Prevalence and Progress of Non-alcoholic Fatty Liver Disease (NAFLD)/Non-alcoholic Steatohepatitis (NASH) in Chinese

Nonalcoholic fatty liver disease (NAFLD) is a progressive liver disease ranging from simple steatosis to cirrhosis of the liver. Nonalcoholic fatty liver (NAFL) without substantial hepatocellular injury is thought to be relatively benign whereas nonalcoholic steatohepatitis (NASH) is characterized by hepatocyte steatosis, ballooning, inflammation and varying degrees of fibrosis from none to cirrhosis. NASH is strongly associated with insulin resistance and metabolic syndrome and thus is recognized as a major public health concern as the most prevalent liver disease. Liver biopsy is the gold standard for a diagnosis of NASH. However, given the large population of patients at risk for NASH, liver biopsy is not a practical method for determining which patients may benefit from NASH therapy. Non-invasive methods to estimate inflammation and fibrosis are in clinical use, but there remains a dichotomy between gold standard inclusion criteria and end points that are utilized in clinical trials and real world diagnostic methods that are more common in clinical practice. Thus, the investigators would like to conduct an observational study to head-to-head compare the non-invasive methods and liver biopsy in differential liver steatosis and liver biopsy in a real-world setting. Also, by following up patients for a relatively long time (proposed 10 years), the investigators can present the natural history of disease progression.

NCT03282305 Nonalcoholic Fatty Liver Nonalcoholic Steatohepatitis
MeSH: Fatty Liv Fatty Liver Non-alcoholic Fatty Liver Disease
HPO: Hepatic steatosis

Exclusion Criteria: - Unable to provide written informed consent (or assent in pediatric subjects) - Alcohol consumption greater than 21 units/week for males or 14 units/week for females (one unit of alcohol is half pint of beer [285 mL; 9.64 oz], 1 glass of spirits [25 mL; 0.85 oz] or 1 glass of wine [125 mL; 4.23 oz] - Enrolled in NASH-related clinical trials - Presence of other forms of chronic liver disease: 1. Chronic hepatitis B (HBsAg positive) 2. Chronic hepatitis C (HCV RNA positive) 3. Iron overload disorders (3-4+ iron on liver biopsy or known hemochromatosis gene (HFE) C282Y homozygous with ferritin > 200 ng/ml; note: an elevated ferritin alone is common in NASH and is not exclusionary) 4. Autoimmune liver disease (biopsy evidence or clinical diagnosis of autoimmune hepatitis or Primary biliary cholangitis (PBC) requiring ongoing treatment, imaging evidence of Primary sclerosing cholangitis (PSC)) 5. Wilson's disease 6. Alpha-1 antitrypsin mutations that in the opinion of the principal investigator is contributing to the patient's liver disease; - Prior bariatric surgery unless the surgery was performed more than one year before the biopsy diagnosis of NASH (i.e., NASH is present despite prior bariatric surgery); - Planned bariatric surgery (e.g. --- C282Y ---

Primary Outcomes

Description: The change in NASH Clinical Research Network (CRN) score based on liver biopsy

Measure: Histological endpoint

Time: 10 years

Secondary Outcomes

Description: Number of all-cause death

Measure: Number of all-cause death

Time: 10 years

Description: Number of liver-related death

Measure: Number of liver-related death

Time: 10 years

Description: Number of liver transplant

Measure: Number of liver transplant

Time: 10 years

Description: Number of hepatocellular carcinoma (HCC)

Measure: Number of hepatocellular carcinoma (HCC)

Time: 10 years

46 Study of the Association Between Transferrin Saturation and Asthenia in Hemochromatosis

Observational study.

NCT03356548 Hemochromatoses, Genetic
MeSH: Hemochromatosis Asthenia

- Inclusion criteria: - homozygous C282Y ; - in the maintenance phase for at least 6 months ; - follow-up at Rennes University Hospital ; - patient who has not expressed his opposition to participate in the study. --- C282Y ---

Hemochromatoses, Genetic Hemochromatosis Asthenia The linked HFE genetic hemochromatosis (C282Y mutation in the homozygous state) is the most common form of genetic iron overload. --- C282Y ---

Our objective is to evaluate, in patients homozygous C282Y in maintenance phase, the association between quality of life and Transferrin Saturation Coefficient . --- C282Y ---

Primary Outcomes

Measure: Quality of life questionnaire SF 36

Time: Through study completion, an average of 3 months

Measure: Biological markers : Transferrin Saturation Coefficient

Time: Through study completion, an average of 3 months

47 Effects of Polyphenols on Iron Absorption in Iron Overload Disorders.

Dysmetabolic iron overload syndrome and genetic hemochromatosis are frequent causes of iron overload. Polyphenols are efficient iron-chelators. Investigator hypothesize that polyphenol supplementation can reduce iron absorption in iron overload disease. Iron absorption can be studied by the area-under-the-curve of serum iron after iron oral loading. The primary outcome is the decrease of post-prandial serum iron after rich-iron meal, due to polyphenol supplementation.

NCT03453918 Dysmetabolic Iron Overload Syndrome Geneti Genetic Hemochromatosis Iron Absorption Polyphenols Dietary Supplement: polyphenols Other: Placebo
MeSH: Hemochromatosis Iron Overload Syndrome

- For Genetic Haemochromatosis type 1 Group: homozygosity mutation C282Y in HFE gene ; patients undergoing therapeutic phlebotomies. --- C282Y ---

Primary Outcomes

Description: decrease of intestinal iron absorption after standardized oral loading dose through rich-iron meal, expressed by area-under-the-curve of serum iron, due to concomitant administration of a single dose of dietary polyphenos (nutrient complement) versus placebo administration. This outcome is a quantitative variable, treated and analysed as such.

Measure: Decrease of post-prandial iron absorption after dietary polyphenol supplementation

Time: at day 3

Secondary Outcomes

Description: comparison of oxylipin levels, through lipidomic analyses by spectrophotometry

Measure: Post-prandial changes of circulating oxylipin in iron overload diseases after iron-rich meal and effects of polyphenols supplementation

Time: at day 1 (fasting versus 3 hours after rich-iron meal, versus 3 hours after rich-iron meal with polyphenol supplementation)

Description: comparison of oxylipin levels, through lipidomic analyses by spectrophotometry. Healthy subjects datas comes from a previous study (MEPHISTO).

Measure: Comparison of oxylipin levels between DIOS, genetic hemochromatosis and healthy subjects after 6 hours of fasting.

Time: at baseline

48 Testing the Efficacy of a Natural Polyphenol Supplement to Inhibit Dietary Iron Absorption in Subjects With Hereditary Hemochromatosis: a Stable Isotope Study

Polyphenolic compounds are very strong Inhibitors of non-heme iron absorption, as they form insoluble complexes with ferrous iron. Patients with hereditary hemochromatosis (HH) have an increased intestinal non-heme iron absorption due to a genetic mutation in the regulatory pathway, leading to excess iron in the body. This study investigates the inhibitory effect of a natural polyphenol Supplement in participants with HH.

NCT03990181 Iron Metabolism Disorders Iron Overload Polyphenols Dietary Supplement: meal matrix & NPPS Dietary Supplement: meal matrix & CS Dietary Supplement: no-matrix & NPPS Dietary Supplement: no-matrix & CS
MeSH: Hemochromatosis Iron Overload Metabolic Diseases Iron Metabolism Disorders

Inclusion Criteria: - Homozygous for C282Y mutation in HFE (hemochromatosis) gene - Written informed consent - Age 18-65 y - Not pregnant or lactating - Body weight < 75 kg - Body mass index (BMI) between 18.5 and 25 kg/m2 - No acute illness/infection (self-reported) - No metabolic or gastrointestinal disorders, eating disorders or food allergy to the ingredients of the test meal (self-reported) - No scheduled phlebotomy throughout the study period - The last phlebotomy will be at least 4 weeks prior first test meal administration - No use of medications affecting iron absorption or metabolism during the study - No intake of mineral/vitamin supplements 2 weeks before the first study day and during the study - Participation in any other clinical study within the last 30 days - Expected to comply with study protocol Inclusion Criteria: - Homozygous for C282Y mutation in HFE (hemochromatosis) gene - Written informed consent - Age 18-65 y - Not pregnant or lactating - Body weight < 75 kg - Body mass index (BMI) between 18.5 and 25 kg/m2 - No acute illness/infection (self-reported) - No metabolic or gastrointestinal disorders, eating disorders or food allergy to the ingredients of the test meal (self-reported) - No scheduled phlebotomy throughout the study period - The last phlebotomy will be at least 4 weeks prior first test meal administration - No use of medications affecting iron absorption or metabolism during the study - No intake of mineral/vitamin supplements 2 weeks before the first study day and during the study - Participation in any other clinical study within the last 30 days - Expected to comply with study protocol Iron Metabolism Disorders Iron Overload Polyphenols Hemochromatosis Iron Overload Metabolic Diseases Iron Metabolism Disorders null --- C282Y ---

Inclusion Criteria: - Homozygous for C282Y mutation in HFE (hemochromatosis) gene - Written informed consent - Age 18-65 y - Not pregnant or lactating - Body weight < 75 kg - Body mass index (BMI) between 18.5 and 25 kg/m2 - No acute illness/infection (self-reported) - No metabolic or gastrointestinal disorders, eating disorders or food allergy to the ingredients of the test meal (self-reported) - No scheduled phlebotomy throughout the study period - The last phlebotomy will be at least 4 weeks prior first test meal administration - No use of medications affecting iron absorption or metabolism during the study - No intake of mineral/vitamin supplements 2 weeks before the first study day and during the study - Participation in any other clinical study within the last 30 days - Expected to comply with study protocol Inclusion Criteria: - Homozygous for C282Y mutation in HFE (hemochromatosis) gene - Written informed consent - Age 18-65 y - Not pregnant or lactating - Body weight < 75 kg - Body mass index (BMI) between 18.5 and 25 kg/m2 - No acute illness/infection (self-reported) - No metabolic or gastrointestinal disorders, eating disorders or food allergy to the ingredients of the test meal (self-reported) - No scheduled phlebotomy throughout the study period - The last phlebotomy will be at least 4 weeks prior first test meal administration - No use of medications affecting iron absorption or metabolism during the study - No intake of mineral/vitamin supplements 2 weeks before the first study day and during the study - Participation in any other clinical study within the last 30 days - Expected to comply with study protocol Iron Metabolism Disorders Iron Overload Polyphenols Hemochromatosis Iron Overload Metabolic Diseases Iron Metabolism Disorders null --- C282Y --- --- C282Y ---

Primary Outcomes

Description: The change in the isotopic ratio of iron will be measured after administration of a test meal/drink including iron isotopes

Measure: change from baseline in the isotopic ratio of iron in blood at week 2

Time: baseline, 2 weeks

Description: The change in the isotopic ratio of iron will be measured after administration of a test meal/drink including iron isotopes

Measure: change from baseline in the isotopic ratio of iron in blood at week 4

Time: 2 weeks, 4 weeks

Secondary Outcomes

Description: to assess iron status

Measure: Serum Ferritin concentration (µg/L)

Time: baseline, weeks 2, and 4

Description: to assess iron status

Measure: Serum iron concentration (µg/dL)

Time: baseline, weeks 2, and 4

Description: to assess iron status

Measure: Soluble transferrin receptor (mg/L)

Time: baseline, weeks 2, and 4

Description: to calculate percent of transferrin that has iron bound to it; Plasma iron and transferrin saturation will be combined to calculate transferrin saturation (ratio)

Measure: Transferrin saturation in %

Time: baseline, weeks 2, and 4

Description: to assess blood volume based on weight, height, and Hb.

Measure: Hemoglobin (g/dL)

Time: baseline, weeks 2, and 4

Description: identify acute inflammation

Measure: C-reactive Protein (mg/L)

Time: baseline, weeks 2, and 4

Description: identify chronic inflammation

Measure: alpha-1-glycoprotein (g/L)

Time: baseline, weeks 2, and 4

Description: the major regulator of non-heme iron absorption

Measure: Serum Hepcidin (nM)

Time: baseline, and weeks 2

49 Haemochromatosis and Periodontitis

Periodontitis is a chronic inflammatory disease that affects tissues surrounding the teeth. It is strongly associated with the major pathogenic "red complex", including Porphyromonas gingivalis, Tannerella forsythia and Treponema denticola1 and thus is considered an infection. Recent advances in the pathogenesis of periodontal disease have suggested that polymicrobial synergy and microbiota dysbiosis together with a dysregulated immune response can induce inflammation-mediated damage in periodontal tissues2-4. Interestingly, currently periodontitis is associated with a growing number of systemic diseases, including cardiovascular diseases, adverse pregnancy outcomes, diabetes5-7 and hereditary haemochromatosis8.

NCT04006249 to Evaluate the Prevalence of Periodontal Diseases in Patients With Hemochromatosis at the Time of Diagnosis and / or Their Usual Therapeutic Diagnostic Test: dental probes
MeSH: Periodontitis Periodontal Diseases Hemochromatosis
HPO: Periodontitis

Inclusion Criteria: - Patients aged 35 to 64 years with homozygosity hemochromatosis C282Y - Patients regularly enrolled in a health insurance plan - Patients with at least 10 natural teeth - Patients who have given informed written, dated and signed consent Exclusion Criteria: - Diabetic patients - Simultaneous participation in another study - Pregnant or lactating women - The incapacitated persons and persons deprived of their liberty - Patients who do not speak French, both written and spoken - Patients previously included in this trial - Patients with heart valves or endovascular equipment (risk of infective endocarditis ...) - Patients with a history of maxillofacial surgery - Patients whose oral status is considered incompatible with entry into the study, at the discretion of the investigator - Patients on drugs that can cause gingival hypertrophy, such as Hydantoins (phenytoin), Dihydropyridines, Diltiazem or Ciclosporin - Patients on medication that can cause gingival bleeding (anticoagulants, antiplatelet agents and aspirin). --- C282Y ---

Primary Outcomes

Description: To evaluate the prevalence of periodontal diseases in patients with hemochromatosis at the time of diagnosis and / or their usual therapeutic

Measure: prevalence of periodontal diseases

Time: 2 years


HPO Nodes


Hepatic steatosis
Genes 137
ATP7B LDLRAP1 MPV17 CLPB APOE APOB SLC40A1 POLG HNF1B COA8 ABCG8 BSCL2 HFE GPD1 BCS1L CIDEC ACAD9 LYRM4 AGPAT2 LMNA LMNB2 PRDM16 CAV1 FOS LMNA TYMP LIPE RERE BCS1L MPV17 BSCL2 CIDEC MCCC1 ACADM PLIN1 SLC25A13 HADHB ETFA CAV1 XRCC4 CPT1A FBP1 PCK1 PTRH2 CEP19 RMND1 LMNA GABRD POLR3A TMEM199 NSMCE2 PPARG ADK ACAD9 LIPA TFAM NGLY1 PMM2 HNRNPA1 VPS33A AKT2 POLD1 MARS1 DDOST TRAPPC11 ETFB ACADVL BSCL2 ALMS1 LMNA LARS1 CPT2 CBS CARS2 COX15 NDUFAF1 LRPPRC ALDOB PCSK9 HNRNPA2B1 TRMU PGM1 NSMCE2 CPT2 LIPE ACOX1 LDLR CYP7A1 MRPL44 PCK2 DNAJC19 LMNA FARSB ABHD5 CAVIN1 PNPLA2 HADH ZMPSTE24 ETFDH ALMS1 PNPLA2 SLC22A5 PHKG2 AGPAT2 DGUOK ATP6AP1 COG6 ABHD5 HADHA PHKA2 SLC40A1 TARS2 LMNA TRAPPC11 PPARG MRPS7 KCNAB2 ACADL HADH SLC25A13 ACADM VCP HNF4A PLIN1 PPARG EARS2 SAR1B CAVIN1 SLC25A13 HSD17B4 DNAJC19 RRM2B SKI CYP19A1 IARS1 POLG ABCG5
Hepatitis
Genes 90
CD247 CTNNB1 ATP7B CASP10 PIEZO1 GUSB BLNK SHPK CYP7A1 IL17RA IGF2R CASP8 SH2D1A SLC25A15 BTK BTK C4B CD79B VPS33B XIAP SERPINA1 PIK3R1 GLIS3 POU2AF1 CIITA FOXP3 TPP2 RFX5 CIITA RASGRP1 RFXANK SLC25A15 AXIN1 TCF4 CD3D TP53 IL12A PRKCD CD40LG BTK IGHM IL17RC ALMS1 TRAF3IP2 KRT8 FAS LRRC8A FAS IL17F XIAP SPIB C1S RFX5 RFXAP MST1 TTC7A COG8 SKIV2L VIPAS39 IGLL1 PDGFRL TNFSF15 HSD3B7 CD3E AMACR ATP7B FASLG RFXANK IL12RB1 TCF3 CD79A KRT18 IRF5 MET PIK3CA MMEL1 ITCH TBX19 IL21R AIRE RFXAP TTC7A CLEC7A GPR35 ATP7A CYP7B1 STAT1 PGM1 APC TNPO3
Abnormality of the liver
Genes 1378
CLDN1 GPC3 LETM1 MPL PIEZO1 UBR1 TNFRSF11A CLPB IL17RA HNF1B CCDC115 CYP27A1 CTSC TRIM37 BTK AGPAT2 CASP10 ATP8B1 SDCCAG8 HMBS TREX1 POU1F1 C8ORF37 RMRP SF3B1 WDPCP PAX8 KIT CFTR XRCC4 PRKCD NDUFB10 LMNA ATP8B1 TMEM67 KRT8 PCSK1 HMGCL NSMCE2 PEPD CA2 EPB41 NBAS NGLY1 UQCRB TERC IFT172 ABCA1 PMM2 NPHP3 PSAP AP1S1 MARS1 TTC21B TRMT10C CDKN2C LRP5 GBA NDUFAF5 TREX1 CBS WDR19 SUMF1 KRT17 MKS1 PNPLA6 NDUFV2 TINF2 TBX1 IL2RB NPHP4 NPC2 TMEM67 CYP7B1 CEP290 HOXD13 COX8A MMAB BLK MPI PHKB WDR19 ALG8 HIRA TRIM37 GBA CYP7A1 GBE1 ALG9 WDR60 GNPTAB RNASEH2C AP1S1 NRXN1 LMNA CYBA PEX5 KCNH1 LHX3 COX14 ATPAF2 SLC22A5 NDUFS7 TF GDF2 MPC1 SMPD1 PNPLA2 LHX1 PCCB RBPJ PET100 ICOS CTSA CLDN1 PEX5 KMT2E AP1B1 DUOX2 BPGM LZTR1 ASS1 SLC4A1 PTPRC TBX19 HAMP BMPR1A CDKN1C SPIB PIK3C2A ARVCF CALR ATP6V1B2 RAG2 CDAN1 ABCA1 ITCH B3GLCT MST1 COG6 SLC11A2 B9D2 IGF2 CD28 IDUA MRPS7 PEX13 SCYL1 AMACR IGF2 PEX12 JMJD1C IL12RB1 MEN1 MMEL1 FCGR2A NAGA FLI1 HSD17B4 SLC25A20 KRT6B CYP19A1 TTC37 RHAG CD247 RNU4ATAC TNFRSF1A ATP7B TMPRSS6 MET LDLRAP1 GTF2I HADHA BLNK SHPK KIAA0586 IGF2R COA8 PEX2 BCS1L PMS2 ACVRL1 VPS33B IYD UGT1A1 CPA1 HNF4A NCF1 BCS1L TPP2 RNU4ATAC STAT6 PCCA ND4 NGLY1 POLG ND2 ERCC4 PSAP EFL1 PDGFB PIGM ERCC4 RMND1 MIF TSHR BBS7 FANCD2 ALG6 USP18 MRPL3 PEX6 CLCN7 PEX10 ND1 NOS3 MSH2 GATA6 HMBS SMAD4 SNX10 SPRTN PKHD1 BRCA1 ZIC3 WDR35 ALDH7A1 ETFB PEX10 DUOXA2 ACADVL LETM1 TERT KRT18 APOE SMPD1 WHCR FGFR2 PEX11B INVS RPS20 PRKAR1A CR2 HFE MPL SRD5A3 HAVCR2 CC2D2A AKR1D1 HNRNPA2B1 SLC25A13 NHLRC2 COX15 GPC4 MPI DCLRE1C PSMB8 CTNNB1 DDRGK1 LDLR SGSH KRIT1 BTNL2 SAA1 ASL ALG9 PEX16 BTK MSH6 EWSR1 C4B WDR60 HPD COG4 PSAP MKKS BBS5 FANCL ALG13 MYORG HLA-DRB1 FOXF1 MRAS STN1 AGGF1 LHX4 PIGA TGFB1 GPI WRAP53 RNASEH2A TGFBR2 DNAJB11 DNAJC21 FAS APOA1 ZAP70 DCTN4 APC OSTM1 RRM2B C1S IFT140 DPM2 DGUOK BTNL2 GPC3 ABHD5 SOX10 HADHA PEX11B PEX3 SDHA WDR34 TARS2 NDUFAF1 ACVRL1 DYNC2LI1 DLL4 SLC30A10 GATA6 CTSK KLF1 SLC25A13 ATP6 PIK3CA ALG1 DPM2 PPARG COX4I2 TBX19 SLC25A13 RAD51C RMRP FGA ANK1 SLC5A5 NHP2 DLD G6PC3 CSPP1 HJV NDUFB3 APOB SON RASA2 HBA1 MS4A1 SLC25A15 APC LIG4 ACAD9 TFR2 PALLD APOE SOS1 STOX1 RFWD3 RFC2 CTRC LIPE MCCC1 UROS HBA1 HADHB RAF1 NOP10 LIPA RFXANK STXBP2 UROD TNFRSF1B HLA-B SUMF1 TP53 HBG1 SLC37A4 NHP2 FBP1 PCK1 XK TWNK SDHD SLC25A20 TRNN CD55 IDS IL17F MEFV SLC39A8 LTBP3 FANCI GBA RPGRIP1L PRPS1 PSAP DCDC2 HLA-DRB1 NSD2 PEX6 TET2 BSCL2 SLC29A3 ARSA MAD2L2 ABCC2 PEX3 COG2 ATP11C ABCB11 RFXANK LRPPRC SFTPC TMEM216 CFH ITCH PRKAR1A SBDS LYST LZTFL1 PEX14 GPR35 INTU FANCA STAT1 NSMCE2 CYBC1 LBR FGFRL1 CD96 SLX4 CASP10 RAG2 RPGRIP1L TERT MYD88 UGT1A1 IDUA NOTCH2 DPM1 FAN1 CEP55 CLCN7 HAMP BTD CC2D2A MKS1 CEP83 FARSB RNASEH2A BBS2 GCK ELN DNAJC21 CIITA BOLA3 PALB2 GCLC HADHA MKS1 IL7R PKD2 MICOS13 NAGLU SLC25A4 CD46 LBR TMEM67 DIS3L2 MOGS CYP7B1 PNPLA2 ACAT1 CASK ELN UQCRC2 RFX5 SNX10 IL6 COG8 MLH3 JAM3 NDUFV1 CTLA4 CLCN7 ABCB4 PRSS1 WT1 PPARG STEAP3 ADA TG LMNA PLIN1 XYLT1 ZAP70 UFD1 CAVIN1 EIF2AK3 CFTR CC2D2A TNPO3 TWNK GBA NAGS TMEM67 HNF1A F5 TCIRG1 APOE ATP7A FECH WDPCP ATP8B1 NCF1 ND3 NPHP3 RBM8A POLG2 TSC2 NDUFS7 OFD1 LMNA EFL1 UCP2 PEX13 SLCO1B1 MCM4 ESCO2 CLCN7 CTC1 SDHB MSH6 APC CEP290 PLPBP NOTCH1 PEX12 CYC1 CD70 CASR DOCK6 PLG TMEM70 KCNH1 ARSA LRRC8A FAS ICOS DCDC2 RNF43 PLEKHM1 TCTN2 TFAM VPS33A UGT1A1 HBG2 G6PC TTC8 ALMS1 NCF2 PDX1 GLB1 LIPT1 TNFRSF13C B9D1 PEX5 GANAB CARS2 BBIP1 PEX11B FADD CD79A SLC4A1 BRCA1 RNASEH2B TRNS1 TRNE H19 NEK8 BRCA2 CFTR AIRE NCF2 POLG2 APC F5 NDUFS3 APC TERC DPAGT1 CCND1 HLA-DRB1 CEL MYC PROP1 ALDOA GPC4 NR1H4 ARL6 MVK TRHR DDRGK1 HNF1A CBS DAXX TET2 MVK EOGT DNAJC19 PEX16 TTC21B C8ORF37 IFT27 PIK3R1 TERT SCARB2 LBR PC ADAR HNF4A FAH PEX14 IL36RN TANGO2 BBS1 PEX2 POLG2 NPHP3 PEX1 TCF4 HBA2 PIGS SLCO1B3 TRNK ACOX1 NPHP1 PEX26 PTPN3 WDR19 PEX2 SEMA4A MFN2 TINF2 ETFDH APPL1 GNPTAB PSAP RAG2 AGPAT2 RFXAP HBB USP9X NFKB1 FANCC KCNJ11 IL2RG CNTNAP2 LMNA GYS2 PKHD1 RECQL4 ERCC8 GBA AMACR KRT18 HMGCS2 MYBPC3 GUSB VCP PEX13 SP110 PRKCSH CDKN1B TET2 CSPP1 MMUT UBE2T FBP1 RRM2B KIF23 JAK2 PEX1 IER3IP1 DZIP1L SPINK1 ND5 GUSB SBDS PEX1 FERMT3 ABCG8 LYRM4 B2M JAK2 DPM3 NLRP3 POU2AF1 BRCA2 TYMP LYZ PKD1 PEX12 BSCL2 RFX5 IDUA HBB RASGRP1 NOP10 HYMAI HYOU1 CASR ENG DHCR7 HBA2 IFT172 NUBPL PTRH2 CEP19 KCNN3 CC2D2A TMEM199 RPGRIP1L PEX19 ADK SEC63 WT1 SURF1 ERCC4 HNRNPA1 VIPAS39 RRAS2 BCS1L KLF1 GPC1 TCIRG1 RELA COX6B1 HSD3B7 CPT2 COX15 TSHR IFNGR1 CPT2 PKLR PLAGL1 FANCF ND2 SDHA HEXB NRAS RFXAP KLF11 MECP2 INPP5E TRMU NDUFA11 IFIH1 H19-ICR ASAH1 SLC7A7 TRIM28 SLCO2A1 CLCA4 MLXIPL CLIP2 BMP2 BRCA2 DMD DPM3 POU6F2 DHFR CTBP1 STEAP3 PARS2 SERPINA1 NDUFS2 SPTA1 PRF1 ABCB4 INSR LIG4 CEP290 PAX8 ABCD3 KCNN4 TMEM107 SDCCAG8 CIITA SEC23B MUC5B PRSS1 NPM1 ITK MSH2 SEC63 SRP54 IFIH1 XPR1 IFT172 SLC13A5 STX11 JAK2 TBL2 ALMS1 KRT6A COX20 ABCG8 BSCL2 SLC17A5 NPHP3 TRMT5 COG7 FAH PHKG2 ABCC2 POMC TNFRSF13C SEC24C FANCG IDUA IL2RG PEX26 GALNS SLC40A1 FUCA1 TRAPPC11 TSFM SPTB CD3E GNE TCF3 SLC29A3 PEX3 COMT CA2 SAR1B AGA CDKN2A CLEC7A SKI SPTB POLG KRAS GPC3 SMPD1 REST SPTA1 SLC7A7 AKT2 IFT122 PEX14 SPECC1L FAM111B EPB42 GYPC HFE GPD1 SLC20A2 PEX10 CORIN GNS ALAS2 CD79B PEX6 PRDM16 FOS BBS10 PDGFRA SLC30A10 NDUFAF3 MPV17 HADHA GBA IL1RN GBA BBS1 GNAS HBB SLC25A15 CAV1 XRCC4 CPT1A PEX13 FANCB KRAS STX1A FECH RAD51 SCYL1 TNFRSF13B MMUT LIPA NDUFS1 GABRD ANTXR1 ADAMTSL2 GP1BB PEX14 POLR3A COG1 SKIV2L VPS13A PFKM RFT1 KRAS ARSA SMAD4 PPARG DIS3L2 INPPL1 NDUFS4 ACAD9 AP3B1 NOTCH2 NLRP3 GATA2 TTC7A SC5D AKT2 SKIV2L JAK3 DDOST ADAMTS13 PRKCSH PAX4 RTEL1 VHL FASTKD2 HBB NEK1 NDUFA6 ALG8 RPGRIP1 ATP7B NPHP1 INSR IL7R OFD1 SPTB CDKN1A CASR PEX1 XRCC2 CD19 PEX10 ALDOB TRIM28 PCSK9 RPGRIP1L ANKS6 CYBB PSAP TPO PSMB4 CPT2 LIPE WT1 APOC2 IFT80 PTPN11 KIT ARSB SP110 AGL HSD3B7 NDUFS6 ASAH1 PEX19 SOS2 CFTR KCNQ1OT1 NKX2-5 CD27 PEX12 RFT1 RRAS NDUFB9 LPIN2 RREB1 GCGR TGFB1 PEPD UNC13D RNU4ATAC STK11 DOLK LONP1 TIMMDC1 APC IL12A BTK BCS1L PDGFRA SCO1 FOXRED1 PHKG2 CD81 EPB42 DKC1 SMAD4 STK11 PRKCD ACSF3 C11ORF95 ATP6AP1 IFT80 COX10 CEP290 NLRP1 TMEM126B HBG2 NLRC4 COX10 DYNC2H1 PDGFRL TNFSF12 KAT6B FLT1 TMEM216 ADA FASLG IFT43 NDUFAF2 TREX1 CTRC DNAJC19 BMPER SPINK1 RIT1 BBS9 ERCC6 NDUFA1 MPV17 TMEM67 BAZ1B POLG KRAS TRNW LACC1 GALK1 ARHGAP31 COA8 ND6 BSCL2 HNF1A CIDEC FASLG INS NFKB2 WDR35 ABCC8 TRNV NEU1 RERE IQCB1 PLEKHM1 DLL4 ACADM SLC25A13 RHAG ETFA TRMU SLC26A4 GBA TACO1 CPT1A TNFSF11 HNF1B IL17RC FAN1 TBX1 UGT1A1 NEUROD1 RBCK1 GTF2IRD1 CDKN2B HK1 CTNNB1 POLD1 G6PD IFT140 ERBB3 C1QBP PARN LARS1 ALG11 ARSA HELLPAR PMM2 TNFSF15 LCAT ICOS TNFSF12 DMPK GLRX5 USB1 NAGA FAS IL21R TTC7A SLC39A4 AGA FBN1 PYGL MYRF PRSS2 ENG MLH1 ABCC8 CTNS PCCB PEX3 TALDO1 HPGD NDUFAF4 NPHP3 SLC4A1 ALDOB CCDC47 JAG1 COG5 PKLR TNFRSF13B COG8 MRPS16 TSC1 ALG2 FBXL4 EIF2AK3 FUCA1 NPC1 CPOX GLB1 NEUROG3 KCNQ1 GLIS3 VPS45 ABHD5 EXTL3 WDR34 CAVIN1 PTEN TRIM32 GBA FGFR2 CFI PEX26 TALDO1 HBB AXIN1 SRD5A3 KCNJ11 UGT1A1 COG4 IDUA FANCE FANCM IGHM SLC2A1 TRAF3IP2 PEX6 HJV TRAF3IP1 HNF1B TP53 POU1F1 CEP120 SLC22A5 PSMB8 TNFRSF1B SLC25A19 DNASE1L3 PEX26 PDGFRB SLC37A4 HMOX1 HGSNAT SETBP1 CR2 ACADL CEP164 TMEM165 HADH SFTPA2 MET AP3D1 ACADM LRP5 HNF4A H19 NDUFB11 EARS2 PEX3 PMS1 BRAF ATP7A BBS12 IFT172 TJP2 KRT16 ABCG5 DYNC2H1 GDF2 AHCY CD19 ACADVL GUCY2D HMGCL DLD TNFSF11 CYBB GNMT TRIP13 SLC40A1 GAA CYBA DHDDS ABCB4 RAG1 TREX1 TTC37 JAK2 MLH1 PSMB9 NSD2 WDR35 SLCO1B1 LMNA LMNB2 SDHC TERC CAV1 RAG1 PEX1 OCLN HBB FOXP3 CIDEC PLIN1 LYST PEX5 BCHE A2ML1 INPP5E ABCG8 CD3D CYP27A1 COG2 MMAA CPLX1 TRNW PEX2 SETBP1 CTLA4 DCLRE1C HESX1 TGFB1 CTLA4 XIAP IL7R LIPA TMEM67 NOD2 NELFA IL2RG RFX6 EPB41 RAG1 TRAPPC11 SLC25A1 RHBDF2 IGLL1 PIK3CA POMC LMNA SERPINA1 LIMK1 GALE TSHB ABCB11 DYNC2LI1 NDUFAF1 GALT SLC2A1 CCDC28B GALT ANK1 SC5D SLC35A2 TRNL1 PEX12 WDR19 DHCR7 AKR1D1 PGM1 IL2RA TMEM231 ND1 BLVRA NDUFS8 ACOX1 ATM FDX2 MRPL44 IKZF1 PRKCD ATRX CASP8 HFE MYH9 SH2D1A PEX16 PCK2 PEX19 H19 ADA2 RHAG HNF4A NAB2 XIAP CDKN1B CHD7 LPL FH ALAS2 C15ORF41 TRAF3IP1 HADH RNASEH2C EPCAM SLC25A19 PEX16 PEX6 NHP2 CD40LG ZMPSTE24 PHKA2 RAB27A SRP54 DKC1 TPI1 TUFM CD28 ND3 GLB1 DGUOK MMUT GPIHBP1 PEX19 HADHB NCF4 NRAS PALB2 BRIP1 AUH PHKA2 TCIRG1 YARS2 BBS4 ABCA1 GFM1 SLCO1B3 KCNAB2 PCCA MAN2B1 IRF5 APOA1 KRT8 CP TBX1 GNE CPT2 NDUFS4 GCDH TERT SAMHD1 IARS1
Chronic hepatitis
Genes 11
ALMS1 KRT8 IL21R AIRE RFXAP C4B RFXANK CD40LG KRT18 RFX5 CIITA
Iron deficiency anemia
Genes 19
PLA2G4A CD55 ABCD3 FOXP3 STK11 CLCNKB ATRX KCNQ1 CLPX FAS HBB DAXX WAS SLC12A3 APC FASLG KCNE1 CASP10 ALAS2
Hepatic fibrosis
Genes 140
CSPP1 TTC37 DYNC2H1 BBS9 TMEM67 MET IFT122 DZIP1L TMEM67 SLC40A1 WDPCP ARHGAP31 ABCB4 TTC37 GPD1 WDR35 NPHP3 POU2AF1 BBS10 SDCCAG8 C8ORF37 IQCB1 DLL4 PLIN1 BBS1 WDPCP SLC25A13 CEP290 NOP10 INPP5E NOTCH1 SCYL1 PTRH2 DOCK6 TMEM67 BBS7 CC2D2A SKIV2L RPGRIP1L DCDC2 TCTN2 LIPA TMEM67 IFT172 PMM2 NPHP3 RPGRIP1L CTNNB1 AP1S1 PKHD1 WDR35 GPC1 TTC8 NEK1 B9D1 PMM2 TNFSF15 RPGRIP1 NPHP1 BBIP1 INSR FADD INVS OFD1 CCDC28B PEX1 MKS1 PNPLA6 NEK8 CC2D2A LZTFL1 INPP5E RPGRIP1L ANKS6 GPR35 NPHP4 TMEM67 CEP290 MPI TMEM231 IFT80 MPI ARL6 AGL WDR60 CEP55 ASL ALG9 CC2D2A EOGT BBS2 MKKS IFT27 GLIS3 BBS5 INSR CEP290 TRIM32 ABCD3 TRAF3IP1 TMEM107 SDCCAG8 BBS1 DOLK MKS1 RBPJ TALDO1 TCF4 IL12A NPHP1 NHP2 WDR19 TMEM67 HJV HAMP TRAF3IP1 CYP7B1 NPHP3 SPIB PHKG2 IFT140 DGUOK MST1 B9D2 PHKA2 SLC40A1 WDR34 BBS4 PKHD1 TMEM216 SCYL1 DLL4 CEP164 IL12RB1 IRF5 MMEL1 BBS12 IFT172 CC2D2A TNPO3
Anemia
Genes 722
GTF2H5 PIEZO1 ERCC6L2 TNFRSF11A HBA2 MECOM RPL18 EPHB4 SBDS RPL35A BIRC3 FERMT3 COX15 ATRX OPA1 NFKB1 CTC1 JAK2 CASP10 NLRP3 TET2 TYMP GREM1 ZBTB24 ATRX LAMA3 FAM111A RFX5 SLC40A1 RMRP SF3B1 SBDS HBB RASGRP1 KIT HYOU1 CASR PRKCD ENG SURF1 HBB HBA2 COQ2 PIGA NPHP4 SLC19A3 IRF2BP2 HMGCL FANCG TNFRSF4 PEPD CA2 EPB41 HBA1 TERC ERCC4 ABCA1 WAS MARS1 REN KLF1 TCIRG1 BMPR1A HBB PARN GBA COX6B1 ENG COL7A1 PLA2G4A TBCE IFNGR1 PKLR RPS14 FANCF RPL15 TNFAIP3 TINF2 NRAS LARS2 WFS1 RFXAP ADA2 RPS7 IL2RB SURF1 COX8A MMAB RPS7 IL12B RPS17 SMAD4 ALG8 SLC7A7 SLC19A2 SLCO2A1 HLA-B CD3G ORAI1 TBL1XR1 DHFR STEAP3 FIP1L1 SLC4A1 SPTA1 COX14 PRF1 AGXT TF COL7A1 SPTA1 SAMD9 ABCD3 KCNN4 PGK1 NDUFS2 CIITA SEC23B BCOR NDUFS1 PET100 NPM1 ITK SRP54 BPGM STX11 SLC4A1 SLC46A1 DNASE1 COX20 PLEC PLEC RPS28 NABP1 CALR CLCN7 RAG2 CDAN1 PHKG2 TNFRSF13C HBG1 CFH RPL31 FANCG FCGR2A IL2RG NDUFAF2 COG6 CCND1 SLC11A2 PHGDH NUMA1 IFNG SPTB ITGB4 RPS26 GATA1 HPRT1 ELANE RPS27 SLC29A3 ISCU MMP1 HELLS CA2 FLI1 SPTB STAT3 POLG KRAS RHAG SPTA1 STIM1 ATP7B SLC7A7 ITGA2B RPL11 SHPK HBB-LCR GP1BA FOXP1 EPB42 COA8 GYPC MYSM1 MPL RPS26 FANCA LAMB3 ALAS2 ACVRL1 MPLKIP AMN ABCB7 GATA1 NHEJ1 TPP2 GBA HBB LRBA DNMT3B SDHA ALAS2 CP FANCB EFL1 FECH RAD51 PRKACG C1R MMUT RMRP DBH FANCD2 PFKM CLCN7 SMAD4 TACO1 XRCC4 LCAT NPHP1 PRF1 NLRP3 SMAD4 SNX10 TTC7A FANCB RPL5 ADAMTS13 BRCA1 COL17A1 RTEL1 AMMECR1 PACS2 FASTKD2 ALAD AK1 HBB NDUFAF5 SMPD1 SPP1 HBA2 NDUFB8 IDH1 HBB ATP7B CTLA4 GATA1 GATA1 CAD NPM1 SPTB SLX4 XRCC2 FTCD MPL SRD5A3 FOXP3 CD59 NHLRC2 DCLRE1C PSMB8 PSMB4 GCLC KIT MTR TMPRSS6 SP110 SMAD4 HBA1 RPL5 NDUFA12 EWSR1 NDUFA13 PGM3 FANCC IDH2 SLC46A1 LPIN2 FANCL TP53 UNC13D AGGF1 STK11 GTF2E2 C1QA TGFB1 RPL35 APC GSS GPI WRAP53 BTK DGKE PDGFRA DNAJC21 FAS SCO1 MTFMT TINF2 ABCB7 RPS29 ITGB3 CD81 EPB42 DKC1 OSTM1 STK11 IFT140 PRKCD RPS19 SAMD9L BTNL2 SPTA1 COX10 RPL15 NLRP1 HBG2 NLRC4 RPS15A CRIPT SDHA PHGDH GLA TNFSF12 ACVRL1 ADA SPTA1 ZBTB16 FASLG CTSK STIM1 FOXRED1 KLF1 COL7A1 CLCNKB SFXN4 HBB COX4I2 SLC25A13 RAD51C DNAJC19 RMRP ANK1 STAT5B C3 GATA1 PRDX1 G6PC3 COL7A1 RPL35A YARS2 DDX41 BCL10 NDUFA4 NPHP4 ERCC2 AK2 CLPX HBA1 COA8 ECHS1 RPL11 MS4A1 FASLG LIG4 TFR2 NFKB2 FANCD2 PUS1 TBXAS1 TARS1 AASS IREB2 KIF15 RFWD3 ATRX TERT NDUFAF3 PLEKHM1 HBA1 PTEN UROS WIPF1 HBA1 ATRX NDUFS3 RHAG NOP10 LIPA LMBRD1 THRA GBA TRNT1 HLA-B HBD TACO1 IRX5 RPL27 SEC61A1 TNFSF11 SLC19A2 HBG1 NHP2 PCNT ALX4 BMPR1A NDUFS4 PTPN22 TRNN CD55 STAT4 HK1 PML ANK1 FANCI NT5C3A BMPR1A UMPS NDUFS7 G6PD CFB LAT LYRM7 ERBB3 PARN NBN HSPA9 TET2 RARA LARS1 RNF113A MAD2L2 HELLPAR TEK ATP11C BRCA1 ICOS RFXANK ELMO2 GATA1 TNFSF12 ELANE PTH1R GLRX5 USB1 EPO CFH FAS SMARCAL1 SBDS LYST HPRT1 FMO3 RPL26 TTC7A ENG FANCA STAT1 MUC1 PCCB TALDO1 HPGD SLX4 CASP10 TET2 RAG2 TERT SLC4A1 MYD88 GLA PKLR ACD TNFRSF13B KDM6A CLCN7 PTF1A ACVR1 RPS10 HAMP SAMD9L FARSB CPOX RPS10 NDUFS2 DNAJC21 SMARCAL1 VPS45 KMT2D TGFB1 GBA PALB2 CFI GCLC PUS1 TALDO1 HBB SRD5A3 PIGT CD46 FANCE FANCM TMEM67 SLC4A1 NPHP1 DNM1L SLC2A1 RPL26 CFI WFS1 RAG1 LIG4 UMPS CASK PGM3 ADAR PSMB8 PDHA1 SNX10 MTRR DKC1 PNP WT1 HMOX1 COG1 CR2 STEAP3 ADA COL7A1 FARS2 LAMC2 ZAP70 CUBN ALPL F2 ETV6 TCN2 STAT3 NBN RPS15A CFHR1 GDF2 ITGB4 CD19 HMGCL UROD TNFSF11 MMADHC TCIRG1 FECH NDUFA2 ABCD4 TREX1 RAG1 PSMB9 COL4A1 CDCA7 TF RBM8A KRT14 SDHC TERC EXT2 LPIN2 RAG1 TFRC EFL1 TSR2 PFKM HBB RPS29 FOXP3 FANCE CLCN7 CTC1 SDHB LYST KIF1B PNPO TBXAS1 HAVCR2 ABCG8 MMAA NDUFAF6 TRNW FAM111A DCLRE1C FAS HBB TERT RPS27 NSUN2 CTLA4 XIAP PLEKHM1 IL7R NOD2 GSS VPS33A HBG2 NDUFA10 PRKAR1A FCGR2B EPB41 RAG1 NDUFV2 HBA2 THBD CISD2 ERCC3 TERC NDUFV1 SLC4A1 GNA14 GALT SLC2A1 ZBTB20 CFHR3 TRNS1 RPS19 STAT1 ANK1 BRCA2 AIRE RPL27 SLC25A38 WAS IL2RA PGK1 HLA-DRB1 LIPT1 HBB RPS24 FDX2 ALDOA IKZF1 PRKCD RPS24 LAMA3 ATRX KCNQ1 DAXX UBE2T SH2D1A SLC12A3 ACAD8 MVK DNAJC19 MTHFD1 UBR1 ADA2 RHAG LAMC2 SCO2 MPIG6B SCARB2 CHD7 IGH OCRL NDUFA9 ALAS2 C15ORF41 RPS14 GPX1 SMARCD2 STING1 HBA2 CD40LG CD46 CBLIF TINF2 SRP54 DKC1 TPI1 ABCB6 GATA1 ACTN4 RECQL4 PSAP RAG2 IRAK1 BMPR1A HBB MAD2L2 NFKB1 PET100 FANCC TSR2 MALT1 UROS BRIP1 FANCL PHKA2 TCIRG1 YARS2 ABCA1 SARS2 MTRR FERMT1 RPS17 PCCA PNPO GBA MMP1 TRNT1 APOA1 MMACHC CP LAMB3 TET2 RPS28 MMUT STIM1 UBE2T RTEL1 RRM2B KIF23 TERT KCNE1 NDUFS8 PHF21A MLX
Periodontitis
Genes 41
PLG GORAB PLG DKC1 FGF3 CTSC CTSC AP3B1 SLC35C1 ELANE NOTCH2 CTSC PLG RTEL1 CXCR4 TERC PARN GFI1 TCIRG1 FERMT1 OCRL ELANE C1S SRP54 ITGB2 C1R USB1 CTC1 LYST NOP10 COL3A1 NPM1 WRAP53 C1S TERT COL3A1 C1R NHP2 CTSC TINF2 FERMT1
Insulin resistance
Genes 122
LIPC KCNJ11 HNF1A GCGR STAT3 BSCL2 HSD3B2 ABCC8 AGPAT2 INS LMNA LMNB2 LMNA PDX1 ABCC8 ABCC8 INS CAV1 FOS ZMPSTE24 LMNA HYMAI LIPE BSCL2 CIDEC PLIN1 PPARG HYMAI CAV1 XRCC4 ADCY3 SLC2A2 CEP19 IGFALS LMNA MAPK8IP1 TCF7L2 DBH NEUROD1 NSMCE2 AKT2 PPARG XRCC4 IGF1 GATA6 NEUROD1 GCK AKT2 POLD1 PAX4 BSCL2 ALMS1 LMNA PDX1 PMM2 KCNJ11 HNF1A PTF1A HYMAI PLAGL1 HNF1B KLF11 NSMCE2 PIK3R1 BLK LIPE KCNJ11 GPD2 HMGA1 CEL INSR INSR ZFP57 CAV1 LEP ABCC8 SLC12A3 SLC30A8 EIF2AK3 LMNA GCK PDX1 RETN PDX1 CAVIN1 HNF4A IRS1 PIK3R1 ZFP57 PLAGL1 LEPR KCNJ11 ZMPSTE24 GCK MFN2 WFS1 ALMS1 APPL1 DCAF17 ABCC8 PAX4 ZMPSTE24 HSD11B1 AGPAT2 ENPP1 IRS2 HNF4A WRN PTPN1 PPP1R3A LMNA PAX4 PPARG IGF2BP2 KCNJ11 LMNA MTNR1B CLCNKB PPARG CAVIN1 EIF2AK3 CYP19A1
Lymphoproliferative disorder
Genes 9
KRAS ZAP70 MYD88 NRAS IL2RG MYD88 CD70 MCM4 CD27
Abnormality of blood and blood-forming tissues
Genes 1848
PIEZO1 TNFRSF11A HBA2 BIRC3 PRKAR1A KIT COL5A1 ATRX CYP11B1 CASP10 PIGL F2 TET2 ATRX LMBRD1 LAMA3 SLC40A1 KIT GLI1 PROC HMCN1 PEPD EPB41 CASP10 NBAS NGLY1 ABCA1 NEDD4L WAS MARS1 REN ENPP1 PLG LRP5 GBA TREX1 DYNC2LI1 RPS14 TNFAIP3 TINF2 TYROBP ADAMTS2 NPC2 CYP7B1 BLK KCNJ11 CYB5A HIRA SLC19A2 GP1BA RNASEH2C ANKRD26 SLC22A4 CD3G BUB1B TAF1A DOCK8 GDF2 HLCS SPTA1 SMPD1 BCOR HLA-DPB1 NDUFS1 PET100 BCR APP JAK2 SSR4 IL10 IFNG SLC17A5 MLLT10 BCL11B NOTCH3 BMPR1A CALR RAG2 CDAN1 FCGR2A NDUFAF2 COG6 SUFU RUNX1 ACP2 IFNG ITGB4 SDHC HPRT1 ISCU COL5A1 MTTP SMAD3 TGFBR1 CD247 MET IGH GFI1B ATP6V0A2 COA8 DNMT3A VWF RPS26 ACVRL1 VPS33B GATA1 FOXE3 NCF1 TAL1 RECQL4 SMAD4 TPP2 RNU4ATAC ITGA2B SDHA SH2B3 PRKACG PDGFB PIGM ERCC4 C1R RMRP ALG6 WIPF1 CD81 F7 ADAMTS2 NOS3 GATA6 CHD7 SMAD4 SRP72 DOCK8 FLI1 BRCA1 TAZ SLC2A1 TERT HBA2 NDUFB8 HBB GATA1 TMPO MTOR MTHFR CR2 HAVCR2 SERPINF2 MYH6 SDHB AKR1D1 CD59 NHLRC2 MPI DCLRE1C GLB1 TMPRSS6 KRIT1 STK4 NEBL SAA1 NDUFA12 EWSR1 COG4 ACTN1 MYORG SDHD EPHB2 MRAS AGGF1 GTF2E2 SMAD3 ESCO2 TGFB1 GPI PDGFRB RNASEH2A CEBPE TGFBR2 DGKE MTFMT APC ABCB7 ITGB3 FCGR2C KIT F9 ABHD5 RAD54L GFI1 SPATA5 GLA SLC30A10 MAP2K2 NDP PIK3R1 CTSK STIM1 KLF1 VHL COL7A1 CST3 SFXN4 HBB DPM2 SLC25A13 RAD51C RMRP ANK1 KCNJ11 CD40 DLD LRP5 ATM COL5A2 RPL35A PSEN1 BCL10 LPP CCR1 ERCC2 GP1BA HBA1 JAK2 ACAD9 TFR2 FANCD2 ATP6V0A2 IREB2 KIF15 SOS1 NEXN STT3B F11 ATRX CTRC TGFBR2 PTPN11 HPS3 HBA1 PTEN RS1 WIPF1 NDUFS3 TNFRSF1B LBR SLC37A4 CXCR4 KIT TNFRSF13B CYSLTR2 CORO1A TRNQ PTPN22 TRNN CD55 ALG12 MEFV CCM2 SCARB2 FANCI GP9 NT5C3A UMPS WAS CD247 ANKRD1 GFI1B AK2 MAD2L2 RFXANK ELMO2 CARD11 PTH1R ACTC1 MYH11 SMARCAL1 JAGN1 LYST MSH2 GPR35 FANCA NSMCE2 CYBC1 HLA-DPA1 LBR ANKRD11 SLX4 RAG2 KRT14 DPM1 CLCN7 FARSB RNASEH2A SPARC CISD2 DNAJC21 TGFBR2 ADA PLVAP AKT1 KMT2D NOTCH1 GCLC TNFRSF1A IL7R IL10 FUT8 RFWD3 TMEM67 NPHP1 BRAF CYP7B1 ACAT1 RFX5 ITGB3 MTRR MLH3 MLF1 PRSS1 POLE ACSL4 FARS2 RASA1 MTAP VPS13B CUBN ALPL IGHM SDHB CFTR PALB2 COL3A1 GFI1 GBA HNF1A F5 MMADHC ATP7A FECH ABCD4 ACD ITGB3 HRG ZNF469 TREX1 NCF1 LPIN2 GGCX CD3E BUB1 TBXAS1 EFL1 SGCG MCM4 ERAP1 CLCN7 MSH6 GNAQ COPA HAVCR2 NOTCH1 PEX12 SH3GL1 F13A1 SPINK1 IGH DOCK6 HABP2 LRRC8A TERT RPS27 RNF43 ITGB3 RARA GSS HBG2 FCGR2B TNNC1 NCF2 NLRP3 PDX1 TNFRSF13C ERCC3 WAS EVC CTLA4 MYPN CD79A BLOC1S6 CCND1 ZBTB20 TRNS1 BRCA2 AIRE NCF2 TERC CCND1 HLA-DRB1 HBB RPS24 NR1H4 KRT5 MVK ACP5 TXNRD2 DAXX NUP214 TET2 TINF2 ACAD8 MVK EOGT KRT14 DNAJC19 MTHFD1 PEX16 ND1 PIK3R1 OCRL ADAR PIK3R1 MPL PRLR TMEM127 MYH9 TCF4 GNAS HBA2 SEMA4A A4GALT FCGR2C WDR19 APPL1 RUNX1 ACTN4 C4A PSAP BMPR1A B4GALT1 NFKB1 FANCC SRC MEFV RPS17 KRT14 RIN2 VCL KIF1B GBA MVK TRNT1 PLN MMUT UBE2T KLHDC8B FGA RANBP2 GTF2H5 SPINK1 SBDS FERMT3 CYP2C9 COX15 ARPC1B SPINK5 NLRP3 COG4 FHL2 RNF168 SGCD ZBTB24 NTHL1 PEX12 GINS1 TERT HYOU1 CASR NPHP4 IRF2BP2 MMACHC FANCG SEC63 CSF3R BAP1 ERCC4 CDKN2A LRP5 PLOD1 PDE11A PLAT KLF1 TCIRG1 PARN BCR HSD3B7 COL7A1 IFNGR1 PKLR RPL15 RFXAP TRMU SLC4A4 RPS17 SDHB ASAH1 SLC7A7 GP1BA SLCO2A1 DNMT3A HLA-B ORAI1 DHFR STEAP3 FIP1L1 SLC4A1 SPTA1 CALR BAP1 LAMTOR2 PRF1 SERAC1 KCNN4 ABCC8 LCK NPM1 ITK TAL2 IFIH1 TNXB COL5A1 AMMECR1 COX20 ATP7A FANCI FAH JAK2 PHKG2 GALC TNFRSF13C SEC24C RPL31 TGFB2 ITGA2 IL2RG CCND1 NUMA1 FUCA1 ATR FLI1 APP MMP1 CA2 CACNA1D SPTB KRAS SMPD1 TUBB1 SPTA1 VHL CAPN5 RPL11 HBB-LCR GP1BA PEX14 TBX2 EPB42 GYPC SMARCB1 CORIN DOCK2 FANCA LAMB3 CD79B AMN LYST ABCB7 GNAQ DTNBP1 PDGFRA SLC30A10 GBA GBA LMAN1 GNAS HBB PROC STS FANCB FECH MMUT DBH PFKM RFT1 KRIT1 KRAS SMAD4 TACO1 AP3B1 LCAT NLRP3 GATA2 SEMA3E ATM RPL5 ADAMTS13 AMMECR1 PACS2 FASTKD2 HBB SPP1 PRF1 ATP7B GCNT2 SPTB ARHGEF1 CASR KCNE5 ALDOB CD3D CYB5R3 F13B BEST1 BCL10 PSMB4 CPT2 GCLC PTPN22 PDCD10 COX1 COL14A1 SP110 TERT NUMA1 CFTR C4A NDUFA13 PRKACA CD27 FANCC IDH2 SLC46A1 EVC2 RFT1 LPIN2 TCAP TGFB2 FOXN1 RREB1 RNU4ATAC STK11 SCN11A APC TET2 SDHA BTK PDGFRA SCO1 CD81 RET PANK2 PRKCD ATP6AP1 COX10 NLRP1 HBG2 PHGDH PTPN11 TNFSF12 KAT6B FLT1 ADA EGLN1 KRAS CLCNKB PRTN3 COL3A1 SLC39A13 FGB DNAJC19 RIT1 KIT KRT5 GP1BB LDB3 DDX41 NDUFA4 NPHP4 CLPX F13A1 RPL11 NUP214 NFKB2 CLCN7 TARS1 ND4 MYH7 GNAS TERT DLL4 CALR NDUFAF3 PLEKHM1 COL4A1 LMBRD1 THRA GBA TACO1 IRX5 ATOH7 SEC61A1 TNFSF11 SLC19A2 KLF1 IDH2 TBX1 NEUROD1 THPO PML PANK2 ANK1 GATA2 NPM1 NDUFS7 CACNA1S G6PD LAT SOS1 LYRM7 ANGPTL6 GFI1 NBN TNNI3 LARS1 APP GATA1 USB1 FAS HPRT1 TBXA2R F10 TAZ MLH1 MUC1 HPGD COL3A1 FGG GNB1 PROS1 ACD KDM6A ALG2 FBXL4 FYB1 NPC1 CPOX USP8 GLB1 CYP11B2 IL10RA ABCC9 EXTL3 TET2 JAK2 GBA FGFR2 CFI COL1A2 WRAP53 GP6 TALDO1 HBB SRD5A3 KCNJ11 PIGT ABL1 FANCE COL3A1 FANCM MAX PRKG1 IGHM RAF1 FLNA F12 CFI PGM3 CYP4F22 AAGAB IL12A PSMB8 PDHA1 TNFRSF1B PSEN2 PDGFRB PNP APOE CR2 TMEM165 LAMC2 BRAF FAT4 F8 CD19 SALL4 UROD TNFSF11 PTPN22 AKT1 SLC2A10 SGPL1 CYBA TTC37 JAK2 PSMB9 GP1BB KRT14 TERC EXT2 F13B TRAC TSR2 PFKM OCLN HBB NLRC4 FANCE LYST HBG1 TBXAS1 ABCG8 TGFB3 CYP2A6 APOB TRNW FAM111A NDE1 DCLRE1C TPM1 IL7R COL4A5 NOD2 ARFGEF2 NDUFA10 IL2RG RAG1 PIK3CA DNM2 TCF4 TERC NDUFV1 GNA14 GALT SLC2A1 STAT1 ANK1 FANCF SLC25A38 AKR1D1 WAS PGM1 IL2RA PGK1 LIPT1 ATM CRYAB STAT4 IKZF1 ATRX SLC35C1 SH2B3 MYH9 SH2D1A CCND1 VPS13A CDC42 UBR1 ADA2 SCO2 CYP26C1 NDUFA9 ASXL1 ALAS2 HLA-DRB1 C15ORF41 RPS14 GATA2 CDH23 NBN EPCAM NHP2 MMADHC CBLIF SRP54 DKC1 TPI1 RECQL4 CD28 GLB1 IRAK1 DGUOK MMUT BLOC1S3 ENG TGFBR3 ABCC6 TSR2 PTEN NCF4 NRAS PHKA2 FERMT1 MAN2B1 FLT3 SERPINF2 MMP1 PICALM PIK3CD APOA1 CP LAMB3 IVD GNE ATRX STIM1 IKBKG TERT SAMHD1 RBM8A DNMT3B PHF21A NFKB2 TMTC3 MPL RPL18 CLPB FLNA ETV6 TP63 RTEL1 OPA1 CTC1 TREX1 PROS1 STAT3 RMRP SF3B1 CFTR SERPINE1 COL4A1 DOLK SLC25A11 XRCC4 PRKCD HBB CCM2 COQ2 PIGA CFHR1 MPL LRP5 HMGCL TNFRSF4 CA2 FZD4 TERC PMM2 HTRA2 KIT RAB27A CBS PLA2G4A GUCY1A1 VKORC1 WFS1 RPS7 IL2RB COX8A MMAB ALG8 NUTM1 DIAPH1 RBM20 TP53 LEP PUF60 TRNF CYBA TBL1XR1 EP300 COX14 GNA11 F5 TF COL7A1 TINF2 RBPJ THBD ICOS CLDN1 KIF11 PEX5 BPGM PLAU LZTR1 SLC4A1 SLC46A1 PTPRC FGB RYR1 PLEC RPS28 ARVCF CLCN7 NBN MST1 CFH SLC11A2 FGG TMEM127 CD28 HAX1 MRPS7 CD8A AMACR RAF1 SDHA CHST14 JMJD1C ND5 ELANE HELLS APC FLI1 HPS5 STAT3 ADAM17 TTC37 RHAG ATP7B BLNK SHPK CYB5A BLNK FOXP1 MAT2A F7 BUB1B PEX2 GNAQ PMS2 MSH6 ACTN2 MPLKIP AIP POMP CPA1 ITGB2 BCS1L LRBA DNMT3B EFL1 VHL RPSA RUNX1 FANCD2 DES USP18 CLCN7 BRD4 XRCC4 MSH2 NPHP1 SNX10 JAK2 MAP2K1 COL17A1 ALAD AK1 APOE NDUFAF5 SMPD1 ITGA2B IDH1 CTLA4 SCN10A PEX11B SDHD GATA1 NPM1 RPS20 SLX4 USP8 PRKAR1A PROC JAK2 MPL SRD5A3 FOXP3 COL1A1 PSMB8 FGA MTR HPS4 HBA1 CSRP3 MSH6 CCBE1 OTULIN PGM3 SCN9A FANCL FLNA HLA-DRB1 COX3 FLNA TP53 RBM10 STN1 SDHD CIITA GSS WRAP53 TET2 HLA-B RAC2 COX2 DNAJC21 FAS TINF2 EPAS1 RPS29 LIG4 OSTM1 MAP1B IFT140 RPS19 SSR4 GP1BA BTNL2 SPTA1 CRIPT SDHA GDNF STAT3 ACVRL1 SPTA1 PTEN DLL4 ZBTB16 FOXRED1 GNAS ABCC6 COX4I2 RB1 RNASEH2B STAT5B NLRP3 NHP2 GATA1 G6PC3 COL7A1 LIG4 NF1 YARS2 COL1A1 AK2 RASA2 SLC35A1 MS4A1 LIG4 PUS1 NRAS APOE STOX1 RFWD3 GGCX PADI4 UROS HBA1 ANO6 RAF1 NOP10 LIPA RFXANK STXBP2 TRNT1 HLA-B HBD HBG1 NHP2 GSN PCNT VWF HOXA11 ALX4 BMPR1A NDUFS4 XK PIGL STAT4 CYB5R3 GBA F9 XYLT2 EPG5 HSPA9 TET2 SLC29A3 ABCC2 PEX3 ATP11C NAXD BRCA1 GATAD1 BMPR2 ELANE EPO CFH ITCH RET SBDS KLKB1 RPL26 HOXA11 BCR STAT1 SLC35A1 CASP10 TERT TRIP13 MYD88 GLA CYCS GP9 ACVR1 COLGALT1 HAMP PTEN CD244 TNXB RPS10 GCK SMARCAL1 COL4A2 CIITA BCL2 ZNF341 MAX PALB2 PUS1 TGFB3 LEPR RAG2 CD46 SLC27A4 IKBKG ETHE1 PDGFB LAMTOR2 RPL26 ITGA2B RAG1 CBFB BLM UMPS INHBA CASK CALR IL23R VPS13B SNX10 SLFN14 PIK3CA CTLA4 ND6 STT3B WT1 COG1 STEAP3 ADA ATP7A LMNA KCNQ1 DLST ZAP70 LOX UFD1 F2 EIF2AK3 TCF3 STAT3 RAG2 TAZ NBN EPO RPS15A NAGS TCIRG1 RYR1 SDHAF2 F13A1 FADD CXCR4 RBM8A NF2 CARD11 ATP6V1A LMNA FLT3 PEX13 RPS29 F10 CTC1 SDHB NF1 KIF1B PNPO CD70 MPL TPMT MPL FAS ICOS HBB NSD1 PLEKHM1 TFAM SH2B3 SDHC VPS33A CYP4V2 G6PC PRKAR1A THBD MPDU1 CISD2 SLC4A1 C1R RNASEH2B RPS19 ARMC5 PDE4D DPAGT1 CAPN3 CEL MYC TP53 ALDOA PLOD3 CBS FGB RAG1 CEBPA SCARB2 LBR HNF4A GPX1 UBE2A ACTA2 KRAS RAC2 UBAC2 TINF2 CD4 PDCD10 RAG2 CTNNB1 RFXAP HBB MAD2L2 PET100 PRF1 COL1A1 FKBP14 SRSF2 SARS2 ERMARD PNPO FGA FGA MMACHC MYD88 PRKCSH TET2 CTRC RTEL1 EPOR RRM2B KIF23 GATA1 TONSL JAK2 RHOH DCLRE1C ERCC6L2 MECOM EPHB4 RPL35A TBC1D24 MSN NIPBL NFKB1 NFIX JAK2 SF3B1 TYMP F2 COL5A2 DSG2 GREM1 ARF1 FAM111A RFX5 SBDS HBB RASGRP1 NOP10 GATA2 ENG SURF1 C1GALT1C1 IRAK4 HBA2 MECOM SLC19A3 MPL PEX19 AEBP1 CLPB HBA1 CBL FKBP14 LBR RRAS2 FN1 GPC1 IL2RG PSTPIP1 BMPR1A HBB KRT5 COX6B1 ENG TBCE ATP6V1E1 MFAP5 FANCF NRAS LARS2 KLF11 ADA2 GCDH SURF1 RPS7 IL12B FOXN1 IFIH1 PLOD1 SMAD4 MDM2 USB1 MYH7 LIG4 PRDM5 AGXT SAMD9 ABCD3 SCN5A PGK1 NDUFS2 CIITA SEC23B PRSS1 MSH2 SRP54 APP CLN3 XPR1 CFHR3 STX11 FGG DNASE1 PLEC SLC17A5 IL12A-AS1 THPO NABP1 TSC1 HBG1 FH FANCG PHGDH DNAJC21 TCN2 SPTB RPS26 SLC39A13 GATA1 CD3E ELANE RPS27 TCF3 SLC29A3 MYBPC3 F9 COMT SAR1B CD151 AGA ABL1 BMS1 POLG KRT1 STIM1 BCL11B PLEC SLC7A7 ITGA2B CST3 SERPINC1 MGAT2 MYSM1 TRNH SLC20A2 PEX10 IDH1 MPL ALAS2 GP1BB APP DMD SRP54 NHEJ1 TRNL1 SLC25A15 ALAS2 CP MAGT1 RAD51 TNFRSF13B PRLR TREM2 GP1BB SBDS SKIV2L VPS13A ACAD9 PRF1 TTC7A SC5D FANCB JAK3 CHIC2 DDOST PAX4 RTEL1 VHL NLRP12 TRNS1 TDP2 BRAF CAD IL7R XRCC2 CD19 FTCD CYBB RIN2 PTPN11 KIT KCNJ1 PLEC HSD3B7 SMAD4 RPL5 SOS2 BRCA2 TCF4 RRAS SERPINC1 TRNW F11 UNC13D DOLK C1QA RPL35 TSC2 KLRC4 KIF1B P2RY12 IKZF1 ADAMTS3 EPB42 DKC1 STK11 ELANE SAMD9L RPL15 NLRC4 RPS15A FASLG CREBBP GATA2 CTRC XYLT1 PPCS HBG2 SPINK1 ETHE1 C3 PRKAR1A PRDX1 KCNJ5 RPL18 FBN1 KRAS ARHGAP31 PRSS2 COA8 ECHS1 NBEAL2 FASLG INS ABCC8 TBXAS1 PTPN22 AASS TCIRG1 NEU1 VKORC1 SLC2A1 ATRX BAG3 RHAG RPL27 FAN1 CBL HK1 CTNNB1 BMPR1A CFB ERBB3 SALL4 PTPN11 PARN ITGA2 RARA FGG RNF113A HELLPAR PMM2 ABCC6 TEK ICOS TNFSF12 CHEK2 FZD4 GLRX5 MDH2 FMO3 TTC7A PRSS2 ENG PCCB TALDO1 TET2 HPS6 SLC4A1 AGK ALDOB PKLR TNFRSF13B MYC COG8 PTF1A COL1A2 RPS10 SAMD9L BCL10 HBB POT1 NDUFS2 VPS45 ABHD5 WAS PTEN TGFB1 SIK3 PEX26 BUB3 AMMECR1 HLCS RAD54B SLC4A1 DNM1L MYLK SLC2A1 WFS1 LIG4 NFKBIL1 ADAR DNASE1L3 CAP2 PLEC MPO ELN DKC1 HMOX1 SETBP1 TTN COL7A1 AP3D1 PKLR ETV6 PMS1 TCN2 FGB ATP7A TEK FIG4 F5 CFHR1 GDF2 ITGB4 AHCY CARD9 RASGRP2 HMGCL CYBB NDUFA2 RAG1 TREX1 MLH1 COL4A1 CTPS1 CDCA7 TNNT2 LMNB2 TF SDHC RAG1 PEX1 FKTN CD79A TFRC C1S PRDM16 PIEZO1 FOXP3 KIT A2ML1 CD3D PROS1 MMAA NDUFAF6 ARL6IP6 CTLA4 NSUN2 CTLA4 XIAP TRNS2 LIPA BCL6 EPB41 NDUFV2 HBA2 RHBDF2 IGLL1 FBN1 HPS1 UNC119 ARHGAP26 JAK2 RAG1 ERF SH2B3 CFHR3 PARN GALT SC5D FAS RPL27 TLR4 SF3B1 FDX2 PRKCD RPS24 LAMA3 KCNQ1 UBE2T C2 TERT SLC12A3 CD109 RHAG LAMC2 MCFD2 XIAP MPIG6B GGCX CHD7 IGH BLM SERPIND1 FH LAMA4 HADH RNASEH2C SMARCD2 B2M STING1 TGFBR1 CD36 PEX6 CD40LG ZMPSTE24 CD46 ITGB4 BRIP1 RAB27A ADA2 ABCB6 GATA1 NBEAL2 SAMHD1 MLH1 PRSS1 PMS2 ASXL1 MALT1 UROS BRIP1 FANCL TCIRG1 YARS2 ABCA1 MTRR PCCA CEP57 VWF TP53 TBX1 RPS28 KCNE1 NDUFS8 SMAD3 MLX
Leukemia
Genes 190
ATM KRAS KIT RPS15A NF1 MPL RPL35A RPL11 RPL18 DDX41 SBDS LPP ETV6 BUB1B F13A1 DNMT3A JAK2 NUP214 FANCD2 MSH6 FANCA PIGL NRAS TCIRG1 BUB1 TET2 FLT3 TAL1 ATRX TREX1 PDGFRA SRP54 RPS29 PTPN11 CALR FANCE WIPF1 SF3B1 GATA2 GLI1 STS SH3GL1 XRCC4 MPL SH2B3 EFL1 PIGA TREM2 CBL MPL RUNX1 MPL PIGL THPO FANCG NSD1 BRD4 NSUN2 SH2B3 RARA GATA2 NPM1 CBL CHIC2 ERBB3 GFI1 TERT KIT BCR ARHGAP26 DYNC2LI1 EVC SCN10A GATA1 ELANE RNASEH2B RPS14 SH2B3 JAK2 RPL15 SBDS NRAS RPL26 RPL27 ADA2 RPS7 TYROBP F13B MSH2 BCR WAS TERC TP53 TRIP13 MYD88 NUTM1 RPS24 GNB1 TP53 DNMT3A TERT NUMA1 NUP214 RPL5 SAMD9L TET2 CFTR POT1 FANCC RPS10 EP300 EVC2 BUB1B CEBPA BRCA2 DNAJC21 CALR SCN9A LIG4 ADAR BLM TET2 JAK2 SMPD1 RNASEH2C SCN11A GATA2 BUB3 PRSS1 KIF11 BCR RPL35 TAL2 SRP54 IFIH1 ABL1 PDGFRB KRAS RNASEH2A TET2 MLLT10 SRP54 DNAJC21 DKC1 RUNX1 APC LIG4 CBFB BLM THPO CALR NBN JAK2 MLH1 RPS19 ELANE SAMD9L RPL31 PMS2 ASXL1 TSR2 MLF1 PIK3CA DNAJC21 RUNX1 GFI1 SRSF2 SETBP1 HAX1 RPS26 RPS17 FLT3 RPS27 PIK3R1 KRAS CEP57 PICALM CREBBP GATA2 CTRC MYD88 TET2 RPS28 ABL1 RB1 SPINK1 GATA1 NBN JAK2 SAMHD1
Diabetes mellitus
Genes 523
PDE6A IDH3A UBR1 IER3IP1 SPINK1 HNF1B PCARE ND1 OPA1 RP1 AGPAT2 TRNS1 MMP2 TTC8 PDX1 TGIF1 TREX1 CDON CFTR MKRN3 GCK INS PPARG HYMAI COX2 XRCC4 SNRNP200 NUBPL PTRH2 CEP19 NDUFB10 PROKR2 EYS LMNA TRNQ MAPK8IP1 LEPR TCF7L2 NSMCE2 PRPF4 ARL6 RDH12 ARL3 FGF8 GCK KDSR CEL DISP1 NR2E3 NDUFAF5 ARL2BP ERGIC1 PLAGL1 PRPF31 PNPLA6 NDUFV2 COX3 PRCD RLBP1 WFS1 KLF11 TRNL1 PDX1 NDUFA11 BLK KCNJ11 GPD2 SLC19A2 DHDDS MLXIPL LEP CLIP2 BMP2 BRCA2 TRNF IFT140 LMNA RP2 REEP6 NDUFS2 PDX1 PDE4D LIG4 RETN CNGA1 GLI2 NDP PNPLA2 EDA CYTB LHX1 PRSS1 NPM1 IFIH1 TBL2 ALMS1 GCK PRPH2 HAMP DCAF17 ABCC8 SNORD115-1 PRPF8 ENPP1 GUCA1B MEN1 MST1 NEUROD1 POMGNT1 HNF4A PTPN1 PPP1R3A FXN AIP KIAA1549 IGF2BP2 NKX2-5 EIF2S3 COX1 SLC29A3 ND5 SUFU CDKN2A HERC2 FXN CYP19A1 STAT3 MKKS SOX2 LIPC INSR GTF2I TDGF1 GCGR HMGA2 TWNK HFE TRNH HLA-DRB1 CORIN PRPF6 ZNF408 FGFR1 PROM1 FOS ZMPSTE24 PEX1 CPA1 HNF4A NPAP1 NDUFAF3 DLL1 BEST1 TRNK TRNL1 POLG CAV1 XRCC4 ND2 TUB CP SLC2A2 KRAS EFL1 NDUFS1 HNF1A SIX3 POLR3A RP9 TRNE AKT2 NODAL PPARG XRCC4 ND1 NDUFS4 GATA6 WRN DCAF17 TTC7A AKT2 RBP3 POC1A PAX4 RTEL1 NDUFA6 TRNS1 KCNJ11 INSR GJB3 INS CASR USP8 MAK FOXC2 FOXP3 HNF1B GATA3 IMPDH1 APOA5 LIPE TRNL1 LEMD3 IL6 PRKAR1A FGFR1 NDN COX1 FAM161A HESX1 INSR NRL NDUFS6 ABCC8 TRNC CFTR GJA1 PRKACA NDUFB9 TRNW COX3 TTPA GPR101 PLAGL1 TIMMDC1 GJA1 WRAP53 RNASEH2A HNF4A COX2 PAX4 FOXRED1 PAX4 DKC1 RRM2B SMAD4 BLK TMEM126B ND5 NDUFAF1 FLT1 KCNJ11 MAFA GATA6 IL2RA CLCNKB NDUFAF2 CTRC PPARG OFD1 IFT172 SPINK1 PRKAR1A RPGR ATM SNORD116-1 OTX2 NDUFA1 ZFYVE26 NDUFB3 BAZ1B PRSS2 BSCL2 ABCC8 INS WFS1 IFT88 PDE6B GAS1 ABCC8 ABCC8 RGR PALLD ND4 STOX1 GNAS NEK2 RFC2 CA4 HYMAI CTRC LIPE RHO MMP14 SCAPER NOP10 ITPR3 GCK SLC19A2 NHP2 HNF1B CRB1 PEX6 TWNK TRNQ NEUROD1 GTF2IRD1 ABCC8 ND6 DNAJC3 POLD1 GJB4 SPINK1 PARN BSCL2 VANGL1 SLC29A3 PDE11A PTPN22 PTF1A BRAF AHR PWRN1 HYMAI TRNV GLRX5 USB1 HLA-DQB1 ITCH SBDS TRNK GPR35 PRSS2 PROK2 STAT1 NSMCE2 CTNS PIK3R1 NDUFAF4 CDHR1 ZFP57 ATP6 TRNW PTF1A CTNNB1 AIP EIF2AK3 POLA1 GCK TRNE ELN NEUROG3 CISD2 GLIS3 DNAJC21 CAVIN1 ELMO2 PTCH1 ROM1 ZFP57 BBS2 LEPR LRP6 KCNJ11 PRKACA PRPF3 SLC25A4 DNM1L GCK HJV LRAT WFS1 HNF1B TP53 PNPLA2 ELN IRS2 NDUFV1 ND6 PRSS1 CERKL CLRN1 PPARG BBS2 MOG TOPORS ARNT2 FOXH1 RAC1 HNF4A PLIN1 TP53 TRNF NDUFB11 EIF2AK3 CFTR SNRPN USH2A KCNJ11 HNF1A STAT3 C8ORF37 APOE FUZ LMNB2 IGF1R TRNS2 LMNA IPW POLG2 PDX1 TERC SLC16A2 INS CAV1 NDUFS7 AR LMNA HGSNAT KLF11 SEMA4A FOXP3 CIDEC CTC1 PLIN1 IDH3B PCNT PEX10 GCK SPINK1 APPL1 HNF1A ZIC2 ABCA4 FBN1 ZNF513 TRNS2 CRX STUB1 NEUROD1 KLHL7 CISD2 PSTPIP1 ALMS1 LMNA PDX1 LIMK1 HNF1A RPE65 BRCA1 RNASEH2B CCDC28B STAT1 AHI1 AIRE ARMC5 NDUFS3 AGBL5 PDE4D TULP1 SHH DHX38 IL2RA HMGA1 CEL NDUFS8 ATM DNAJC3 INS MAGEL2 HNF1A EDA2R HFE MKRN3-AS1 SLC12A3 SLC30A8 UBR1 ND1 IMPG2 KCNJ11 PWAR1 CNOT1 ADAR BLM PDE8B PDX1 HNF4A IRS1 RNASEH2C INSR PIK3R1 CDH23 BBS1 TCF4 ZMPSTE24 ZBTB20 KIZ TINF2 KCTD1 WFS1 SRP54 APPL1 ND3 WFS1 PRSS1 SPATA7 AGPAT2 HBB MERTK WRN KCNJ11 PALB2 HNF1A LMNA PAX4 SARS2 SLC7A14 SOX3 MC4R PDE6G LMNA ARHGEF18 SAG AMACR MTNR1B CP CNBP PLCD1 CTRC FSCN2 TERT SAMHD1 CNGB1
Portal hypertension
Genes 62
CLDN1 TMEM67 GDF2 MPL HLA-DRB1 SHPK F5 GBE1 SP110 MLXIPL ARHGAP31 JAK2 TET2 CC2D2A EOGT FARSB ADA2 JAK2 ACVRL1 NEUROG3 GLIS3 POU2AF1 GDF2 STN1 DLL4 NPHP3 RBPJ TCF4 INPP5E NOTCH1 IL12A PIGM DOCK6 RPGRIP1L SMAD4 SPIB ELN CALR DGUOK DGUOK RPGRIP1L MST1 DCDC2 BTNL2 PKHD1 TET2 ALMS1 TNFSF15 DLL4 SLC30A10 IL12RB1 IRF5 MMEL1 ITCH MPL GPR35 ENG TMEM67 JAK2 CC2D2A TJP2 TNPO3
Lipodystrophy
Genes 138
LDB3 PSEN1 ATP6V0A2 BSCL2 IGF1R CIDEC PSMB9 AGPAT2 LMNA TNNT2 LMNB2 ATP6V0A2 ACTN2 CAV1 FOS ATP6V1A FKTN FHL2 NEXN ZMPSTE24 LMNA SGCD DSG2 TREX1 LIPE DMD FGFR1 PRDM16 BSCL2 CIDEC PLIN1 BAG3 KCNJ6 DOLK CAV1 B4GALT7 EMD LMNA LMNA KCNJ6 POLR3A DES PDGFRB FBN1 TPM1 PPARG SYNE1 KRAS AKT2 POLD1 DDOST SPRTN FLNA TNNC1 ANKRD1 BSCL2 TNNI3 LMNA PMM2 INSR RBM28 GATAD1 ATP6V1E1 MYPN BANF1 TMPO RNASEH2B ACTC1 USP8 SLC25A24 MYH6 ALB PSMB8 PIK3R1 PSMB4 LIPE CRYAB TMEM43 CLMP NEBL RBM20 CAV1 LMNA TXNRD2 CSRP3 FUCA1 LMNA OTULIN TAF1A FHL1 MYH7 ABCC9 TCAP ADAR FBN1 CAVIN1 LAMA4 SCN5A RNASEH2C LMNA POLR3A PIK3R1 CDH23 DOLK IFIH1 RNASEH2A ZMPSTE24 SDHA PIK3CA ZMPSTE24 FBN1 PSMB8 AGPAT2 ATP6V0A2 CAP2 ALB WRN PSEN2 LMNA LMNA PPARG RAF1 TTN VCL SYNE2 LMNA SLC29A3 MYBPC3 PLN LMNA PLIN1 PPARG CAVIN1 PPCS ACTB TAZ SAMHD1 COL3A1
Biliary cirrhosis
Genes 21
POU2AF1 LBR TNFSF15 DCTN4 NPHP3 IL12RB1 TGFB1 TGFB1 SPIB IRF5 CLCA4 MMEL1 FCGR2A NPHP3 DCDC2 CFTR CFTR WDR35 IL12A STX1A TNPO3
Hypertension
Genes 410
GPC3 MPL PRKAR1A ABCG8 ND1 CYP11B1 TRNS1 B2M MMP2 BRCA2 SDCCAG8 HMBS LYZ PKD1 C8ORF37 BSCL2 WT1 SCNN1B SLC25A11 COX2 CEP19 TRNQ YY1AP1 ECE1 WT1 KCNJ5 ENPP1 FN1 PDE11A HGD SLC25A11 HSD11B2 MFAP5 GUCY1A1 DYRK1B SPRY2 SLC2A10 SMAD6 COX3 SCNN1G SCNN1B LARS2 FOXF1 NPHP4 TRNL1 TMEM67 IL12B HIRA TRIM28 MLXIPL CDH23 CLIP2 HLA-B TRNF POU6F2 NFU1 SDHC CEP290 ENPP1 EDA CYTB SDCCAG8 HLA-DPB1 SCNN1A NKX2-5 COL5A1 LEMD3 YY1AP1 TBL2 ALMS1 NOTCH3 CLCN2 ARVCF SEC24C CFH FH TGFB2 TMEM127 ARMC5 AIP SDHA JMJD1C COX1 ND5 COMT NF1 CACNA1D TGFBR1 REST LDLRAP1 GTF2I PDE3A TNFRSF11B MAT2A HSD11B2 TRNH CORIN SERPINA6 BBS10 AIP MAFB FOXE3 SCN2B SMAD4 CYP11B1 TRNK SLC52A3 TRNL1 CYP17A1 GBA SDHB BBS1 HBB CCR6 XPNPEP3 ERCC4 VHL BBS7 GP1BB TRNE OSGEP PPARG NOS3 TRPC6 HMBS JAK2 VHL KRT18 TRNS1 WT1 NPHP1 SDHD INVS KCTD1 OFD1 USP8 FIG4 TRIM28 LRIG2 PCSK9 SDHB SCNN1G CCN2 COL1A1 TRNL1 WT1 PTPN22 LDLR PRKAR1A COX1 VHL TRNC COQ7 LEMD3 PRKACA MKKS BBS5 SLC52A2 SDHD TRNW COX3 RREB1 GPR101 SMAD3 INVS KIF1B DNAJB11 COX2 APOA1 RET ARHGAP31 KCNJ5 WT1 ND5 GDNF CUL3 GLA FLT1 ACVRL1 TNFRSF11A VHL GNAS PRTN3 COL3A1 ABCC6 XYLT1 CYP11B1 ADAMTSL4 FGA C3 COL5A2 BBS9 ERCC6 KCNJ5 FBN1 APOB BAZ1B PAM16 POU3F4 TMEM70 ND4 STOX1 GNAS RFC2 TGFBR2 CALR IQCB1 CYP21A2 MMP14 SLC37A4 ALX4 TRNQ TBX1 THPO GTF2IRD1 GATA5 ND6 FN1 RPGRIP1L CFB ANGPTL6 RET XYLT2 VANGL1 NR3C1 PDE11A NR3C2 POR TRNK BMPR2 MGP TRNV SUGCT RET MYH11 PRKAR1A MDH2 FMO3 KLHL3 WNK4 TMEM237 LZTFL1 TRNK IRF5 STAT1 NSMCE2 MUC1 COL4A4 HLA-DPA1 GLA IDUA NOTCH2 TRNW CC2D2A SCNN1A NR3C1 CPOX USP8 BBS2 ELN CYP11B2 SMARCAL1 LMX1B BNC2 TRIM32 MAX MKS1 PKD2 LRP6 PRKACA COL3A1 SDHD NPHP1 MAX PRKG1 MYLK HLA-DRB1 DIS3L2 CFI LMX1B ACAT1 ELN EGFR ND6 ELP1 ELN SLC37A4 PPARG CEP164 LMNA PLIN1 DLST TP53 TRNF SMAD4 LOX UFD1 FMR1 SDHB NOTCH1 SMAD4 BBS12 IFT172 ABCG5 MYMK CFHR1 TRIP13 SLC2A10 GJA1 WDPCP FUZ CYP17A1 TRNS2 WDR35 MYH7 SDHAF2 LMNA NPHP3 GUCY1A1 EXT2 HPSE2 OFD1 LMNA FGFR2 MEF2A PLIN1 COL4A3 CEP290 ACTA2 KIF1B CD2AP TGFB3 FBN1 TRNS2 SH2B3 COL4A5 NOD2 SDHC PDE3A G6PC THBD FBN1 CAV1 TTC8 ALMS1 ITGA8 LMNA GANAB LIMK1 BBIP1 CTLA4 BANF1 CCDC28B CFHR3 FBN1 H19 CACNA1H ARMC5 AIP CCND1 ADA2 ARL6 EDA2R CBS SH2B3 TET2 CACNA1D ADA2 ND1 VAC14 IFT27 PDE8B CYP11B1 TRAF3IP1 CDH23 BBS1 TMEM127 COL4A3 GNAS ELP1 ACTA2 NPHP1 MTTP WNK1 WDR19 ZMPSTE24 CD46 GCH1 KCTD1 ADA2 ABCB6 ACTN4 NFIX ENG TGFBR3 ABCC6 WRN LMNA BBS4 PKHD1 FGFR2 MC4R ERCC8 KIF1B KRT8 TBX1 JAK2 PHF21A MLX ABCC6
Immunodeficiency
Genes 257
LETM1 NFKB2 EPG5 BCL10 AK2 MS4A1 RTEL1 IFNGR2 LIG4 NFKB1 AGPAT2 FCGR3A NFKB2 RNF168 TERT ZBTB24 CHD1 ATRX ANTXR2 PKP1 WIPF1 NOP10 GATA2 HYOU1 XRCC4 SDHD NHP2 IRAK4 CORO1A TBX1 RBCK1 MALT1 TNFRSF4 LAT CD247 IL2RG PARN EPG5 BSCL2 PARN AK2 IRF7 ICOS GATA1 TNFSF12 USB1 ACTB SMARCAL1 UNG TYK2 IL21R TTC7A IL2RB STAT1 IKBKG FGFRL1 FOXN1 HIRA CCDC47 CLCA4 ACD TNFRSF13B MYC AICDA IRAK4 CD3G FCN3 CYBA CTBP1 CHD1 LAMTOR2 LIG4 CAVIN1 SIK3 IL7R LCK ICOS NPM1 MYD88 ORAI1 RAG2 CARD11 PTEN IGHM PTPRC LAMTOR2 RAG1 PGM3 ARVCF TNFRSF1B TNFRSF13C IRF8 SEC24C IL2RG COG6 IKBKG CD28 DKC1 POLE CR2 ADA JMJD1C TCF3 AP3D1 MBTPS2 SHANK3 HELLS COMT UFD1 RAG2 TTC37 IFNGR1 BCL11B CD19 CARD9 BLNK PRKDC CR2 BUB1B MEIS2 RAG1 SDHC NSD2 CTPS1 DOCK2 CDCA7 LMNB2 IRF2BP2 CD79B TERC LYST CD19 FOS CD3E TFRC NCF1 NHEJ1 IRF8 CTC1 LYST LRBA DNMT3B CAV1 CRKL STX1A MAGT1 CPLX1 TNFRSF13B MMUT DCLRE1C RMRP GP1BB CTLA4 DCLRE1C SKIV2L LRRC8A CD81 ICOS TGFB1 XIAP XRCC4 IL7R TTC7A SKIV2L TBCE RTEL1 IGLL1 NCF2 IL21 UNC119 SIN3A WHCR TNFRSF13C ISG15 JAK3 CD79A RAG1 USP8 CD19 CR2 STAT1 CD3D CFTR CYBB IL12RB1 WAS AKT1 IL2RA HBB IKBKB ATM STAT1 STK4 PRKCD ACP5 IKBKG SH2D1A MTHFD1 CDC42 ADA2 PGM3 RAG1 XIAP MAPK1 PIK3R1 SLC46A1 CHD7 MS4A1 FOXN1 RREB1 CDH23 KLLN WRAP53 CD40LG SEC23B ZBTB24 PIK3CA BTK FRAS1 TINF2 RAC2 IKZF1 RAB27A DKC1 DCTN4 TINF2 CD81 DKC1 RAG2 PRPS1 NFKB1 IKBKG IL2RG BCR UROS TNFRSF13C POLE SPATA5 TNFSF12 SDHB ADA CUL4B PIK3R1 STIM1 PIK3CD IL12B SP110 NFE2L2 PPARG TBX1 RNF168 AGL RTEL1 RMRP TERT CD40 DNMT3B
Multiple myeloma
Genes 3
LIG4 CCND1 GBA
Lymphoma
Genes 133
ATM KRAS CD19 IGH DDX41 BCL10 BIRC3 FOXP1 MS4A1 TP63 RAG1 LIG4 NFKB2 MSH6 TERC RECQL4 NTHL1 WIPF1 CTC1 LYST NOP10 RASGRP1 TNFRSF1B XRCC4 PRKCD NHP2 MAGT1 TNFRSF13B IGH RMRP RUNX1 CTLA4 DCLRE1C FAS ICOS RNF43 NSUN2 XIAP IL7R CASP10 BCL6 CDKN2A ATM IL2RG RTEL1 PARN NBN KIT TNFRSF13C TCF4 ICOS TNFSF12 CHEK2 USB1 CD19 CR2 NRAS MSH2 WAS BCL10 CASP10 MYD88 COL14A1 PRKCD TNFRSF13B MYC MDM2 SH2D1A CCND1 BCL10 CFTR CD27 PGM3 TCF4 CHD7 IGH LIG4 BLM BCL2 TET2 HLA-DRB1 PRSS1 NPM1 KIF11 ITK WRAP53 RAD54B TINF2 FAS DKC1 APC CD81 LIG4 BLM CD28 DKC1 AAGAB RAG2 TNFRSF1B MLH1 TNFRSF13C DNASE1L3 NFKB1 PMS2 ASXL1 IL2RG PRF1 PTEN MALT1 RAD54L CTLA4 CD28 PNP SRSF2 TNFSF12 STAT3 POLE ADA CR2 ADA FASLG PIK3R1 TP53 CTRC ZAP70 MYD88 RB1 RMRP SPINK1 TERT KLHDC8B NBN RHOH
Myelodysplasia
Genes 93
NAGS MPL SLX4 TET2 TERT TRIP13 DDX41 SBDS TP53 ATRX TET2 SF3B1 BUB1B TCIRG1 DNAJC21 RFWD3 BUB1 TET2 FANCL ATRX ASXL1 TET2 JAK2 SAMD9 SRP54 RPS14 PALB2 GINS1 SMARCD2 GATA2 SF3B1 BUB3 GATA2 SRP54 TET2 FANCB FANCE TET2 FANCM RFWD3 EFL1 RAD51 PIGA SRP54 DNAJC21 RAF1 DKC1 MPL RUNX1 MPL FANCD2 BRAF LIG4 FANCG RECQL4 THPO NBEAL2 CALR JAK2 TERC ERCC4 FANCI ELANE GATA2 SRP72 FANCG ASXL1 FANCC BRCA1 ERBB3 PTPN11 BRIP1 GFI1 SRSF2 HSPA9 KIT HAX1 GFI1B MAD2L2 CEP57 RPS14 FANCF SH2B3 XRCC2 RPS19 TINF2 SBDS TET2 BRCA2 RAD51C UBE2T JAK2 FANCA