SNPMiner Trials by Shray Alag


SNPMiner SNPMiner Trials (Home Page)


Report for Mutation P12A

Developed by Shray Alag, 2020.
SNP Clinical Trial Gene

There are 6 clinical trials

Clinical Trials


1 Gene-diet Interactions

Interactions between genes and environment, i.e. our inherited responses to environmental changes, may be crucial in the development of the common diseases. The investigators were the first to identify PPARG gene as risk gene for type 2 diabetes. The role of the Pro12Ala polymorphism in diabetes risk has also been verified in meta-analysis. However, this effect on seems to depend on intervention and age. In this study the effects of diets high with saturated fatty acids (SAFA) and polyunsaturated fatty acids (PUFA) are compared in subjects carrying either Pro12Pro or Ala12Ala genotype of the PPARG gene. Aim of the study: To test if subjects with Pro12Pro and Ala12Ala genotypes respond differentially to a diet supplemented with high saturated (SAFA) or polyunsaturated fat (PUFA). Hypotheses: 1. Specific: Subjects with the Ala12Ala genotype will be more sensitive to dietary modification, and therefore respond more favorably to PUFA diet 2. More general: Dietary instructions individually tailored according to the genotype would allow better treatment of obesity and diabetes

NCT01274091 Insulin Sensitivity Other: PUFA-diet Other: SAFA-diet
MeSH:Insulin Resistance Hypersensitivity
HPO:Allergy Insulin resistance

The role of the Pro12Ala polymorphism in diabetes risk has also been verified in meta-analysis. --- Pro12Ala ---

Inclusion Criteria: - BMI >20kg/m2 <29kg/m2 - Pro12Pro and Ala12Ala genotypes of PPARG Pro12Ala polymorphism - participation to METSIM-study (METabolic Syndrome in Men, currently >10000 men included from the population living in Kuopio, principal investigator Markku Laakso) - normoglycemia Exclusion Criteria: - type 2 diabetes - other chronic diseases Inclusion Criteria: - BMI >20kg/m2 <29kg/m2 - Pro12Pro and Ala12Ala genotypes of PPARG Pro12Ala polymorphism - participation to METSIM-study (METabolic Syndrome in Men, currently >10000 men included from the population living in Kuopio, principal investigator Markku Laakso) - normoglycemia Exclusion Criteria: - type 2 diabetes - other chronic diseases Insulin Sensitivity Insulin Resistance Hypersensitivity Obesity and type 2 diabetes are increasing in all western countries, including Finland. --- Pro12Ala ---

Inclusion Criteria: - BMI >20kg/m2 <29kg/m2 - Pro12Pro and Ala12Ala genotypes of PPARG Pro12Ala polymorphism - participation to METSIM-study (METabolic Syndrome in Men, currently >10000 men included from the population living in Kuopio, principal investigator Markku Laakso) - normoglycemia Exclusion Criteria: - type 2 diabetes - other chronic diseases Inclusion Criteria: - BMI >20kg/m2 <29kg/m2 - Pro12Pro and Ala12Ala genotypes of PPARG Pro12Ala polymorphism - participation to METSIM-study (METabolic Syndrome in Men, currently >10000 men included from the population living in Kuopio, principal investigator Markku Laakso) - normoglycemia Exclusion Criteria: - type 2 diabetes - other chronic diseases Insulin Sensitivity Insulin Resistance Hypersensitivity Obesity and type 2 diabetes are increasing in all western countries, including Finland. --- Pro12Ala --- --- Pro12Ala ---

The role of the Pro12Ala polymorphism in diabetes risk has also been verified in meta-analysis. --- Pro12Ala ---

Based on these findings the investigators created in collaboration with Johan Auwerx an Pro12Ala animal model that demonstrated a differential effect of dietary fat composition depending on the genotype. --- Pro12Ala ---

However, an important conclusive proof that subjects selected based on their Pro12Ala genotype would respond differently to specifically tailored diet modification is still needed. --- Pro12Ala ---

Primary Outcomes

Description: insulin sensitivity measured by oral glucose tolerance test at the beginning of the first, randomised diet

Measure: insulin sensitivity

Time: week 0

Description: insulin sensitivty measured by oral glucose tolerance test after the first diet

Measure: insulin sensitivity

Time: week 8

Description: Insulin sensitivity measured by oral glucose tolerance test in the beginning of the second, randomised diet

Measure: insulin sensitivity

Time: week 10

Description: insulin sensitivity measured by oral glucose tolerance test after the second diet

Measure: insulin sensitivity

Time: week 18

Secondary Outcomes

Measure: peripheral blood mononuclear cell gene expression

Time: week 8

Measure: peripheral blood mononuclear cell gene expression

Time: week 18

Description: serum lipids, including serum lipidomics and fatty acid composition

Measure: serum lipids

Time: week 8

Description: serum lipids, including serum lipidomics and fatty acid composition

Measure: serum lipids

Time: week 18

Description: inflammation measured as serum cytokines and adipose tissue inflammation

Measure: inflammation

Time: week 8

Description: inflammation measured as serum cytokines and adipose tissue inflammation

Measure: inflammation

Time: week 18

Description: energy expenditure and the rates of substrate oxidation

Measure: energy expenditure

Time: week 8

Description: energy expenditure and the rates of substrate oxidation

Measure: energy expenditure

Time: week 18

Measure: insulin secretion

Time: week 8

Measure: insulin secretion

Time: week 18

Measure: adipose tissue gene expression

Time: week 8

Measure: adipose tissue gene expression

Time: week 18

2 Modulation of Insulin Secretion and Insulin Sensitivity in Bangladeshi Type 2 Diabetic Subjects by an Insulin Sensitizer Pioglitazone and T2DM Association With PPARG Gene Polymorphism.

- The present study was undertaken to assess the efficacy and safety of two different insulin sensitizers (namely Pioglitazone and Metformin) among subjects with type 2 diabetes mellitus (T2DM) in Bangladesh. - A prospective, double-blind, single group, 'within-subject' designed clinical trial of 77 diagnosed T2DM patients out of 130 patients with glycosylated haemoglobin (HbA1c) ≥7.2±1.5%, aged 46±6.4 years and registered for diabetes treatment in Bangladesh Institute of Research and Rehabilitation in Diabetes Endocrine and Metabolic Disorders (BIRDEM) was carried out. - The study was conducted between November 2008 and September 2010. - Baseline data, included case history of the patients,anthropometric measurement, biomedical parameters psychosocial factors, were collected from each subject and then enrolled to receive treatment with 001 drug once daily for three months, then the patients were left for wash out with metformin 850mg once daily for one month; then they received 002 drug once daily for further three months. - Dietary chart was remained as before. - DNA was isolated by Chelex method using the primers and control DNA,restriction Digestion Enzyme Endonuclease Hae 111 for genotyping PPARγ-(Peroxisome Proliferator Activated Receptor gamma)Pro12Pro - (Proline12Proline)/Pro12Ala-(Proline12 Alanine))/Ala12Ala-(Alanine12Alanine). - The blinded drugs were decoded after analyzing results, 001 tablet was pioglitazone (30 mg once daily) and 002 tablets was metformin (850mg once daily). Bio-medical outcomes were measured to assess the efficacy of both the drugs each month. After finishing the treatment period the effects of two drugs were compared using SPSS.And the association between the pioglitazone drug effects and genetic polymorphism was also assessed. - The metformin effects was assessed also using the response rate of HbA1c <7.0% after 3 months treatment to the patients.

NCT01589445 Type 2 Diabetes Mellitus Drug: Pioglitazone hydrochloride Drug: Metformin hydrochloride
MeSH:Diabetes Mellitus Diabetes Mellitus, Type 2
HPO:Diabetes mellitus Type II diabetes mellitus

- DNA was isolated by Chelex method using the primers and control DNA,restriction Digestion Enzyme Endonuclease Hae 111 for genotyping PPARγ-(Peroxisome Proliferator Activated Receptor gamma)Pro12Pro - (Proline12Proline)/Pro12Ala-(Proline12 Alanine))/Ala12Ala-(Alanine12Alanine). - The blinded drugs were decoded after analyzing results, 001 tablet was pioglitazone (30 mg once daily) and 002 tablets was metformin (850mg once daily). --- Pro12Ala ---

We used a published document to select the primers for genotyping PPARγ Pro12Ala/Pro12Pro. --- Pro12Ala ---

The primers for the Pro12Ala SNP genotype, we amplified exon B using the reverse primer 5' CTG GAA GAC AAA CTA CAA GAG 3' and the forward primer 5' ACT CTG GGA GAT TCT CCT ATT GGC 3'. --- Pro12Ala ---

III.Control DNA: Professor Colin Palmer Laboratory, Biomedical Research Institute ,University of Dundee Medical School, University of Dundee, Scotland, UK sent six control samples of 3 types control DNA genotyped for PPARG SNP rs 1801282 (Pro12Ala). --- Pro12Ala ---

5) List of Abbreviations AEs Adverse Events ALT Alanine aminotransferase BMI Body Mass Index BMRC Bangladesh Medical Research Council BIRDEM Bangladesh Institute of Research and Rehabilitation in Diabetes,Endocrine and Metabolic Disorder BP Blood Pressure DNA Deoxynucleic Acid DBP Diastolic Blood Pressure DM Diabetes Mellitus EASD European Association for the Study of Diabetes EDTA Ethylene Diamine Tetra Acetic acid ELISA Enzyme Linked Immunosorbent Assay FBG/FSG Fasting Blood Glucose/Fasting Serum Glucose FSI Fasting Serum Insulin 2hBG 2 hours Blood Glucose HbA1c Glycosylated Haemoglobin HOMA percent B Homeostasis Model Assessment percentage of beta cell function HOMA percent S Homeostasis Model Assessment percentage of sensitivity HOMA IR Homeostasis Model Assessment Insulin Resistance HDL-C High Density Lipid Cholesterol IU/L International Unit/Litre LDL-C Low Density Lipid Cholesterol ml millilitre mm millimetre mg/dl milligram/ decilitre MLR Multiple Logistic Regression OPD Outdoor Patient Department OMIM Online Mendelian Inheritance in Man OR Odds Ratio PPARγ Peroxisome Proliferator Activated Receptor gamma Pro12Pro Proline12Proline Pro12Ala Proline 12 Alanine Ala12Ala Alanine12Alanine PCR Polymerase Chain Reaction QUICKI Quantitative Insulin sensitivity Check Index SD Standard Deviation SPSS Statistical Package for Social Science SBP Systolic Blood Pressure TC Total Cholesterol TG Triglyceride T2DM Type 2 Diabetes Mellitus TZD Thiazolidinedione µl Microliter WHO World Health Organization --- Pro12Ala ---

Primary Outcomes

Description: Response rate was defined by ≥10% decrease of FSG or/and ≥1% decrease of HbA1c from the baseline values after 3 months treatment.48 responded to pioglitazone and 32 responded to metformin.

Measure: Comparison of Changes in Fasting Serum Glucose (FSG)With Pioglitazone and Metformin

Time: 3 months for each drug

Description: Response rate was defined by ≥10% decrease of FSG or/and ≥1% decrease of HbA1c from the baseline values after 3 months treatment.48 responded to pioglitazone and 32 responded to metformin.

Measure: Comparison of Changes in Glycosylated Hemoglobin (HbA1c)With Pioglitazone and Metformin

Time: 3 months for each drug

Description: Response rate was defined by ≥10% decrease of FSG or/and ≥1% decrease of HbA1c from the baseline values after 3 months treatment.48 responded to pioglitazone and 32 responded to metformin. Analysis 1: Homeostasis Model Assessment Insulin Resistance(HOMA IR) Analysis 2: Quantitative Insulin sensitivity Check Index(QUICKI)

Measure: Comparison of Changes in Insulin Levels (HOMA IR,QUICKI) With Pioglitazone and Metformin

Time: 3 months for each drug

Description: Response rate was defined by ≥10% decrease of FSG or/and ≥1% decrease of HbA1c from the baseline values after 3 months treatment.48 responded to pioglitazone and 32 responded to metformin. Analysis 1: Homeostatic Model Assessment of Beta cell function(HOMA percent B) Analysis 2: Homeostatic Model Assessment of Insulin Sensitivity (Homa percent S)

Measure: Comparison of Changes in HOMA Percent B and HOMA Percent S With Pioglitazone and Metformin

Time: 3 months for each drug

Description: Response rate was defined by ≥10% decrease of FSG or/and ≥1% decrease of HbA1c from the baseline values after 3 months treatment.48 responded to pioglitazone and 32 responded to metformin.

Measure: Comparison of Changes in Fasting Serum Insulin (FSI)With Pioglitazone and Metformin

Time: 3 months for each drug

Secondary Outcomes

Description: Response rate was defined by ≥10% decrease of FSG or/and ≥1% decrease of HbA1c from the baseline values after 3 months treatment.48 responded to pioglitazone and 32 responded to metformin. Analysis 1:Total Cholesterol(TC) Analysis 2:Triglyceride(TG) Analysis 3:High Density Lipoprotein(HDL) Analysis 4:Low Density Lipoprotein(LDL)

Measure: Comparison of Changes in Lipid Profiles With Pioglitazone and Metformin

Time: 3 months for each drug

3 Hypocaloric Diet With or Without Microencapsulated Fish Oil or Conjugated Linoleic Acid on Oxidative Stress and Cardiovascular Risk Factors in Women With Metabolic Syndrome Genotyped for Polymorphisms in the Genes PPAR Gamma 2 (Pro12Ala) and Adiponectin (G276T)

Our aim was to assess the effects of a hypocaloric diet, including diet fruit jelly with microencapsulated fish oil or conjugated linoleic acid or placebo, on anthropometry, body composition, insulin resistance and lipid profile in women with metabolic syndrome and genotype Pro12Pro in the PPAR gamma 2 gene.

NCT02183922 Insulin Resistance Oxidative Stress Lipid Profile Blood Pressure Anthropometric Measure Dietary Supplement: microencapsulated conjugated linoleic acid Dietary Supplement: microencapsulated fish oil Dietary Supplement: light fruit jam
MeSH:Metabolic Syndrome Insulin Resistance
HPO:Insulin resistance

Hypocaloric Diet With or Without Microencapsulated Fish Oil or Conjugated Linoleic Acid on Oxidative Stress and Cardiovascular Risk Factors in Women With Metabolic Syndrome Genotyped for Polymorphisms in the Genes PPAR Gamma 2 (Pro12Ala) and Adiponectin (G276T). --- Pro12Ala ---

Primary Outcomes

Description: Plasma malondialdehyde levels

Measure: Oxidative stress biomarker

Time: Change from baseline at 12 weeks

Secondary Outcomes

Description: Homeostatic Model Assessment-Insulin Resistance index, adiponectin, glucose and insulin levels

Measure: Insulin resistance

Time: Change from baseline at 12 weeks

Description: Total cholesterol, LDL-cholesterol, VLDL-cholesterol, HDL-cholesterol and triglycerides serum levels and EPA, DHA and total conjugated linoleic acid plasma levels

Measure: Lipid profile

Time: Change from baseline at 12 weeks

Description: Body weight, body mass index and waist circumference

Measure: Anthropometric measures

Time: Change from baseline at 12 weeks

Description: Fat-free mass and fat mass

Measure: Body composition measures

Time: Change from baseline at 12 weeks

Description: Systolic blood pressure and diastolic blood pressure

Measure: Blood pressure

Time: Change from baseline at 12 weeks

4 Alcohol-related Breast Cancer in Postmenopausal Women - Effect of PPARG2pro12ala Polymorphism on Female Sex-hormone Levels and Interaction With Alcohol Consumption and NSAID Usage

Postmenopausal women, stratified by a peroxisome proliferator-activated receptor gamma-2 (PPARG) polymorphism, were given the following treatments in a random order with a 5w wash-out period: a 400mg ibuprofen tablet or a placebo tablet; both treatments were followed after 30min by a single acute dose of 0.4g alcohol per kg bw. Serum estrogen levels were measured before and at three timepoints after alcohol intake. It is hypothesized that the acute decrease in estrogen sulphate and other markers of estrogens after alcohol intake is modulated by ibuprofen and by PPARG genotype.

NCT02463383 Breast Cancer Drug: Ibuprofen Tab 400 MG Drug: Placebo tab
MeSH:Breast Neoplasms
HPO:Breast carcinoma Neoplasm of the breast

cholesterol lowering medicine); 7. being allergic to alcohol and/or Ibuprofen 8. smoking Breast Cancer Breast Neoplasms In a pilot human intervention trial we aimed to determine the effect of the PPARG Pro12Ala polymorphism and the PPARγ stimulator, Ibuprofen, on sex-hormone levels following alcohol intake in postmenopausal women. --- Pro12Ala ---

Seven women with PPARG Pro12Ala and 18 PPARG wildtype women were included.The study was performed as a randomised, double-blinded, placebo controlled 2x24 h crossover study. --- Pro12Ala ---

Primary Outcomes

Description: Plasma estrone sulfate concentration after acute ethanol intake by Ibuprofen intake and/or PPARG genotype

Measure: Serum estrone sulphate (pmol/l)

Time: from 40 min before to 90 min after alcohol consumption

Secondary Outcomes

Description: Plasma estrone decrease after acute ethanol intake by ibuprofen intake and/or PPARG genotype

Measure: Serum estrone (pmol/l)

Time: from 40 min before to 90 min after alcohol consumption

Description: Plasma SHBG concentration after acute ethanol ingestion by ibuprofen intake and/or PPARG genotype

Measure: Serum SHBG (nmol/l)

Time: from 40 min before to 90 min after alcohol consumption

Description: Plasma ethanol concentration after acute ethanol ingestion

Measure: Serum ethanol (g/l)

Time: from 40 min before to 90 min after alcohol consumption

Description: The plasma metabolome profile by time after alcohol intake

Measure: Serum metabolomics (relative metabolite intensity)

Time: from 40 min before to 24h after alcohol intake

Description: The urine metabolome profile by time after alcohol intake

Measure: Urine metabolomics (relative metabolite intensity)

Time: from 40 min before to 24h after alcohol intake

5 Effect of Nutritional Intervention and Olive Oil in Severe Obesity: Randomized Controlled Trial

Obesity is a worldwide epidemic with increasing prevalence, specially severe obesity (Body Mass Index (BMI) ≥ 35 kg/m2). It is a multifactorial disease that involves genetic and environmental factors that lead to increased mortality from cardiovascular disease, diabetes, cancer, among others and impairs life quality. Most research on severe obesity focuses on surgical alternatives and their results, thus this clinical trial aims to evaluate the effect of a non-pharmacological approach based on nutritional intervention and supplementation with a functional food, the olive oil. It will analyze the effectiveness of interventions on: weight loss, improvements on body composition and inflammatory profile (TNF-alfa, interleucins 1, 6 and 10, adiponectin), insulin resistance and serum lipids control, changing eating habits and physical activity practice, modification on bone mineral density and sarcopenia, and reduction of cardiovascular risk and other diseases. Also, it will be investigated the influence of polymorphisms (Pro12Ala of PPAR-γ gene, -174G>C of IL6 gene e Trp64Arg of ADRB3 gene) on nutritional intervention effectiveness with and without olive oil. This research looks for improving severely obese patient's care and contributing to effective results by reducing costs and risk treatment. The investigators believe that this informations will contribute significantly to the scientific field, expanding the knowledge about severe obesity.

NCT02463435 Severe Obesity Behavioral: Nutritional intervention Other: Nutritional intervention plus olive oil Dietary Supplement: Olive oil
MeSH:Obesity Obesity, Morbid
HPO:Obesity

Also, it will be investigated the influence of polymorphisms (Pro12Ala of PPAR-γ gene, -174G>C of IL6 gene e Trp64Arg of ADRB3 gene) on nutritional intervention effectiveness with and without olive oil. --- Pro12Ala ---

Polymorphism Pro12Ala of Peroxisome Proliferator-Activated Receptor Alfa (PPAR-alfa). --- Pro12Ala ---

Primary Outcomes

Description: Measurements of weight, arm circumference and Body Mass Index (BMI) will be evaluated to assess anthropometric change.

Measure: Anthropometric measurements change

Time: Baseline, week 12

Description: Body fat mass (BFM), body fat percentage (%BF) and body mass density (BMD) will be evaluated to assess body composition change. BFM and %BF will be assessed using multifrequency bioelectrical impedance analysis (BIA) and dual energy X-ray absorptiometry (DXA) and BMD will be assessed using DXA.

Measure: Body composition change

Time: Baseline, week 12

Secondary Outcomes

Description: TNF-alfa, interleucin 6 (IL6), IL1, IL10, adiponectin, C-reactive protein (CRP)

Measure: Change in inflammation parameters

Time: Baseline, week 12

Description: Lipid profile (total cholesterol, LDL-c, HDL-c, VLDL-c), insulin resistance (HOMA-IR, glycated hemoglobin), fasting glycaemia, hemogram

Measure: Change in metabolic parameters

Time: Baseline, week 12

Description: Creatinine, urea and uric acid

Measure: Change in kidney function

Time: Baseline, week 12

Description: AST and ALT

Measure: Change in liver function

Time: Baseline, week 12

Description: TSH, T4 and parathyroid hormone

Measure: Change in thyroid function

Time: Baseline, week 12

Description: Vitamin D, vitamin B12 and folic acid

Measure: Change in vitamins

Time: Baseline, week 12

Description: Iron, calcium, sodium, potassium and zinc

Measure: Change in minerals

Time: Baseline, week 12

Measure: Change in cardiovascular risk using Global Risk Score (GRS)

Time: Baseline, week 12

Measure: Change in cardiovascular risk using Framingham Risk Score (FRS)

Time: Baseline, week 12

Measure: Change in cardiovascular risk using heart rate variability (HRV)

Time: Baseline, week 12

Measure: Change in cardiovascular risk using Homocystein level

Time: Baseline, week 12

Description: Difference in responses between intervention groups for anthropometric measurements (weight, arm circumference and body mass index) and body composition variables (body fat mass and body fat percentage) according to this polymorphism

Measure: Polymorphism Pro12Ala of Peroxisome Proliferator-Activated Receptor Alfa (PPAR-alfa)

Time: Baseline, week12

Description: Difference in responses between intervention groups for anthropometric measurements (weight, arm circumference and body mass index) and body composition variables (body fat mass and body fat percentage) according to this polymorphism

Measure: PolymorphismTrp64Arg of Beta-3 Adrenergic Receptor (ADRB3) gene

Time: Baseline, week12

Description: Difference in responses between intervention groups for anthropometric measurements (weight, arm circumference and body mass index) and body composition variables (body fat mass and body fat percentage) according to this polymorphism

Measure: Polymorphism -174G>C of Interleukin 6 (IL6) gene.

Time: Baseline, week12

Measure: Change in physical activity practice using Global Physical Activity Questionnaire

Time: Baseline, week 12

Measure: Change in physical activity practice using accelerometry

Time: Baseline, week 12

Measure: Change in food intake using Food Frequency Questionnaire

Time: Baseline, week 12

Measure: Change in food intake using 24 hour recall

Time: Baseline, week 12

Description: Change in the following variables: bone density using DXA, falls and fractures and sun exposure

Measure: Change in bone health parameters

Time: Baseline, week 12

Measure: Change in obesity sarcopenia using muscle mass (evaluated using DXA)

Time: Baseline, week 12

Measure: Change in obesity sarcopenia using handgrip strength

Time: Baseline, week 12

Measure: Change in sarcopenia using usual gait speed

Time: Baseline, week 12

Description: It will be evaluated through changes in food consumption (food frequency questionnaire)

Measure: Adherence to nutritional intervention

Time: Baseline, week 12

Description: It will be evaluated through attendance to the clinic visits

Measure: Adherence to the health service

Time: Baseline, week 12

Measure: Change in symptoms of anxiety and depression using Hospital Anxiety and Depression Scale

Time: Baseline, week 12

Measure: Change in symptoms of binge eating disorderusing Binge Eating Disorder Scale

Time: Baseline, week 12

Measure: Change in musculoskeletal pain using Visual Analog Scale

Time: Baseline, week 12

Measure: Change in musculoskeletal pain using Nordic Musculoskeletal Questionnaire

Time: Baseline, week 12

6 Influence of Polymorphysms in the Fto and Ppar Gen Genes, Systemic Inflammation and Oxidative Stress in the Magnitude of Weight Loss Induced by Intermittent or Moderate Continuous High Intensity Training Programs

The study focuses on the influence of polymorphism in the FTO genes rs9939609 and PPARᵧ Pro12Ala, oxidative stress and systemic inflammation on changes in body composition and rest metabolism induced by HIIT and continuous aerobic programs in obese or overweight individuals.

NCT03568773 Overweight and Obesity Chronic Disease Other: High-intensity interval training Other: Aerobic exercise moderate intensity Other: Control Group
MeSH:Overweight Weight Loss Chronic Disease
HPO:Decreased body weight Weight loss

Influence of Genetic and Physiological in Weight Loss The study focuses on the influence of polymorphism in the FTO genes rs9939609 and PPARᵧ Pro12Ala, oxidative stress and systemic inflammation on changes in body composition and rest metabolism induced by HIIT and continuous aerobic programs in obese or overweight individuals. --- Pro12Ala ---

Thus, the objective of the study is to analyze the influence of polymorphism in the genes FTO rs9939609 and PPARᵧ Pro12Ala, oxidative stress and systemic inflammation on changes in body composition and rest metabolism induced by continuous and continuous aerobic programs. --- Pro12Ala ---

Primary Outcomes

Description: The procedure used for analysis is done using a Dual Energy Radiological Absortiometry (DEXA) equipment. The measurement of the body fat and fat free mass percentage measure is obtained by means of a full body scan using the LUNAR PRODIGY DF + 14.319 Radiation (Madison, WI) brand device, following manufacturer's protocols. The body mass is evaluated by means of a balance (Sanny®, São Bernardo do Campo - São Paulo, Brazil), with the volunteer barefoot and in orthostatic position using a Toledo scale sensitive to 100 g. The stature is evaluated by a stadiometer with a tape calibrated at 0.1 of the same mark. Waist circumference and other body perimeters are measured with a 0.1 cm Anthropometric Tape (Sanny®, São Bernardo do Campo - São Paulo, Brazil). Weight and height data are used to calculate BMI using the equation adopted by the WHO: BMI = (Weight / (Stature) 2).

Measure: Body Composition. The changes are being evaluated.

Time: Before the intervention protocol and 48 hours immediately after the last exercise session.

Secondary Outcomes

Description: The metabolic rate was measured using a gas spirometry analyzer. After having fasted from 8:00 pm the previous day, the volunteers were referred to the laboratory shortly after the awakening and were invited to remain seated in a thermoneutral environment for 30 minutes. For the next 30 minutes, VO2, VCO2, VE and RER were monitored until variations of no more than 10% occurred when five-minute intervals were compared. Once this steady state was obtained, these variables were recorded for five minutes. The calculation of the resting metabolic rate is done according to Macdonald (1990).

Measure: Metabolic Rate of Rest. The changes are being evaluated.

Time: Before the intervention protocol and 48 hours immediately after the last exercise session.

Description: Collections of 10 ml of blood from the antecubital vein will be performed early in the morning, with fasting from 10 to 12 hours. The collections will be done 24 hours before, in the 6th week and after the intervention period. They will remain seated for 10 minutes for subsequent collection. Five milliliters of blood will be placed in EDTA-containing test tubes, protected from light and gently homogenized by inversion. The other 5ml will be placed in tubes without anticoagulants. They will then be centrifuged at 3,000 rpm for 10 min. The plasma or serum will be separated, placed in eppendorf tubes and refrigerated at -20 ° C until analysis. All analyzes will be carried out using a commercial kit of the Labtest brand (Minas Gerais-Brazil). The analyzes will be carried out on serum samples using commercial Labtest kits (Minas Gerais, Brazil), following the manufacturer's recommendations and on a Labmax 240 premium automatic analyzer (Lagoa Santa-MG, Brazil).

Measure: Lipid and Glycemic Profile. The changes are being evaluated.

Time: The collections will be done 24 hours before, in the 6th week and 48 hours after the end of the intervention.

Description: 10 ml of blood will be collected in the beginning of the morning, with fasting of 10 to 12 hours, being done 24 hours before, in the 6th week and after the intervention period. Five milliliters of blood will be placed in test tubes containing EDTA and protected from light and the other 5ml will be placed in tubes without anticoagulants and centrifuged at 3,000 rpm for 10 min. The plasma or serum will be separated, placed in eppendorf tubes and refrigerated at -20 ° C until analyzed by a commercial kit of the Labtest brand (Minas Gerais, Brazil). For this, 250 μl of sample will be added to KCl and incubated in a water bath (37 ° / 60 minutes). The mixture will be precipitated with 35% AA perchloric acid and centrifuged at 14,000 rpm for 10 minutes at 4 ° C. The supernatant will be transferred to eppendorfs and 400μl of 0.6% thiobarbituric acid is added and incubated at 95-100 ° C for 30minutes. The material will be read in a spectrophotometer at a wavelength of 532nm.

Measure: Oxidative stress (Malondialdehyde). The changes are being evaluated.

Time: The collections will be done 24 hours before, in the 6th week and 48 hours after the end of the intervention.

Description: 10 ml of blood will be collected in the beginning of the morning, with fasting of 10 to 12 hours, being done 24 hours before, in the 6th week and after the intervention period. Five milliliters of blood will be placed in test tubes containing EDTA and protected from light and the other 5ml will be placed in tubes without anticoagulants and centrifuged at 3,000 rpm for 10 min. The plasma or serum will be separated, placed in eppendorf tubes and refrigerated at -20 ° C until analyzed by a commercial kit of the Labtest brand (Minas Gerais, Brazil). The evaluation of the total antioxidant capacity will be performed through DPPH. For analysis, 100 μl of plasma will be added to 3.9 ml of vortexed DPPH solution, set to stand for 30 minutes and then centrifuged at 10,000 rpm for 15 minutes at 20 ° C. The supernatant will be used for spectrophotometer reading at 515 nm wavelength, using distilled white water. The result will be expressed as a percentage of antioxidant activity.

Measure: Oxidative stress (Total antioxidant capacity). The changes are being evaluated.

Time: The collections will be done 24 hours before, in the 6th week and 48 hours after the end of the intervention.

Description: 10 ml of blood will be collected in the beginning of the morning, with fasting of 10 to 12 hours, being done 24 hours before, in the 6th week and after the intervention period. Five milliliters of blood will be placed in test tubes containing EDTA and protected from light and the other 5ml will be placed in tubes without anticoagulants and centrifuged at 3,000 rpm for 10 min. The plasma or serum will be separated, placed in eppendorf tubes and refrigerated at -20 ° C until analyzed by a commercial kit of the Labtest brand (Minas Gerais, Brazil). The concentration of hs-CRP will be quantified by immunoturbidimetry in serum samples. Calibration will use the Calibra Calibrator from Labtest (Calibra Plus PCR-ultra - Ref-345). Absorbance will be obtained on the Labmax 240 premium automatic analyzer at 540 nm wavelength. The concentrations of hs-CRP will be determined by the commercial kit (Labtest, Minas Gerais, Brazil) according to the manufacturer's instructions.

Measure: Systemic Inflammation (Plasma ultra-sensitive C-reactive protein). The changes are being evaluated.

Time: The collections will be done 24 hours before, in the 6th week and 48 hours after the end of the intervention.

Description: 10 ml of blood will be collected in the beginning of the morning, with fasting of 10 to 12 hours, being done 24 hours before, in the 6th week and after the intervention period. Five milliliters of blood will be placed in test tubes containing EDTA and protected from light and the other 5ml will be placed in tubes without anticoagulants and centrifuged at 3,000 rpm for 10 min. The plasma or serum will be separated, placed in eppendorf tubes and refrigerated at -20 ° C until analyzed by a commercial kit of the Labtest brand (Minas Gerais, Brazil). The A1GPA concentration will be quantified by immunoturbidimetry using the commercial kit (Labtest, Minas Gerais, Brazil) as per manufacturer's instructions. Calibration will use the Calibra Calibrator from Labtest (Calibra Plus Protein - Ref-346). The absorbance will be obtained in the Labmax 240 premium automatic analyzer (Lagoa Santa-MG, Brazil), at wavelength 340nm.

Measure: Systemic Inflammation (Analysis of alpha-1-glycoprotein acid). The changes are being evaluated.

Time: The collections will be done 24 hours before, in the 6th week and 48 hours after the end of the intervention.

Description: Oral cell samples were collected through a mouthwash for 60 seconds of 5 ml of 3% sucrose solution. The resulting contents of the mouthwash were transferred to a 15 ml tube, which immediately afterwards was placed in a solution of TNE (17 mM Tris-HCl pH 8.0, 50 mM NaCl and 7 mM EDTA), diluted to 66% alcohol and autoclaved distilled water.After this, the extraction and genotyping process followed the recommendations of Saiki et al. (1985)

Measure: DNA Extraction and Genotyping

Time: The genetic collection will be made in the 6th week of the intervention.


HPO Nodes


HP:0000819: Diabetes mellitus
Genes 530
IL2RA HGSNAT ABCC8 RP1 APPL1 ND5 TCF4 GPR101 TRNS2 INSR IER3IP1 TWNK RRM2B HYMAI MAK BSCL2 IFT172 SPINK1 BEST1 XRCC4 HNF1B FSCN2 CTRC PWRN1 TRNL1 KCNJ11 ATM STOX1 ABCC8 ENPP1 CRX COX3 BBS2 CRB1 IGF1R PRKACA TINF2 FOXP3 KCNJ11 TRNS1 IRS2 MAFA HNF1B RP9 PDE4D MST1 TRNL1 WFS1 LMNB2 KLF11 GLIS3 SUFU PDE4D ATP6 DNAJC21 PRPF4 KCTD1 ND1 TUB CYTB RHO INS HBB NDUFS1 CLCNKB ZFYVE26 HFE COX2 CTRC INS GCK EIF2AK3 SAG KRAS GLI2 PALB2 CORIN USH2A NHP2 BSCL2 PRPF6 FGF8 PDX1 LIPE RNASEH2A CNGA1 TDGF1 MERTK AEBP1 PDE11A CP PPP1R3A FOS ARHGEF18 PLCD1 SLC29A3 IDH3B LMNA ND1 TRNQ PRPF3 SLC7A14 NDP XRCC4 PAX4 PDX1 MAPK8IP1 ND3 SNORD116-1 SLC2A2 IPW PTF1A INS CEL PAX4 PTF1A LIG4 HMGA2 HMGA1 NDUFS2 TRNS1 RETN POLD1 PPARG ALMS1 PROK2 FGFR1 PCNT INS LRP6 CAT HNF1A CTNNB1 COX2 INSR POLG2 SCAPER PRCD PCARE HYMAI CFTR DHDDS ZIC2 SLC25A4 LEPR BLM GJA1 KCNJ11 ZNF513 FBN1 AKT2 MMP2 LEP ARMC5 CAV1 PTPN22 GUCA1B GCK GCK PDE8B LMNA NEUROG3 FXN GATA6 SLC16A2 SNORD115-1 PAX4 BMP2 TRNL1 AMACR PTPN1 RAC1 PPARG GJA1 FLT1 PNPLA2 ZFP57 BRCA2 STAT1 SLC30A8 SBDS PDX1 POC1A ROM1 C8ORF37 PDE6B DISP1 CTNS PDE6G COX1 ZMPSTE24 IRS1 GCK LIPE ELN ABCC8 FXN DKC1 RGR HNF1A ND5 SIX3 ND4 TREX1 PROM1 SEMA4A CNBP ARL6 MEN1 TRNQ CPA1 HNF1A CAV1 ABCA4 MAGEL2 ELN TULP1 COX1 REEP6 ABCC8 NDUFA11 PLIN1 NDUFAF2 GCK DHX38 WRN HLA-DRB1 GJB4 NDUFB9 FOXP3 LEMD3 PPARG FOXRED1 DLL1 NDUFS7 MMP14 RP2 WRN RLBP1 SARS2 WRAP53 EFL1 RFC2 SLC19A2 NDUFAF1 TERC CFTR ND6 CDKN2A LMNA SPINK1 STAT3 UBR1 CIDEC ND6 DNAJC3 PLIN1 WFS1 ZFP57 ATM STUB1 HNF1B ARL3 IFT88 BRCA1 CEL TRNC OFD1 TERT DCAF17 TRNF NODAL MKRN3-AS1 NDUFA6 PNPLA2 SPINK1 NDUFAF4 PIK3R1 RDH12 STAT3 ND2 ITCH HNF1A FOXC2 APPL1 IDH3A CASR CNOT1 EDA2R PLAGL1 CYP19A1 POMGNT1 INSR AGPAT2 SLC12A3 WFS1 CISD2 GLRX5 HNF4A IL6 LIMK1 LHX1 TBL2 INS BLK PNPLA6 USP8 SLC29A3 RNASEH2B ZMPSTE24 ARL2BP IMPG2 TWNK TRNF TGIF1 GATA3 ZBTB20 RBP3 KIZ SRP54 PRPF8 TOPORS PEX10 DNM1L GJB3 NDUFS4 DNAJC3 ITPR3 RPGR FUZ NDUFS3 SOX2 GATA6 HERC2 PEX1 TRNW PDX1 TKT FAM161A AR LEPR HNF1A NSMCE2 WFS1 IFIH1 ELMO2 ARNT2 TP53 CEP19 NDUFS6 BBS1 FGFR1 HYMAI NDUFAF3 CLIP2 NDUFV1 SLC19A2 INSR NR2E3 MKKS KIAA1549 TMEM126B CP PPP1R15B KLHL7 CNGB1 GCK GCGR PTRH2 MC4R ADAR APOA5 GAS1 TIMMDC1 STAT1 AGBL5 PARN EIF2AK3 SHH FOXH1 NDUFAF5 PROKR2 WFS1 CA4 KDSR SPINK1 HNF1A TRNK KCNJ11 USB1 PAX4 EYS NEK2 PRSS1 CERKL NDUFS8 ND1 LMNA TRNK MKRN3 ERGIC1 BRAF HNF1B MOG RTEL1 POLG CCDC28B CDH23 PEX6 TRNV NDN LMNA NDUFB10 PIK3R1 KCNJ11 ZNF408 HESX1 KCNJ11 UBR1 GNAS PRSS1 ALMS1 HBB BBS2 GCK CDHR1 PRPF31 SMAD4 AIP NEUROD1 HAMP NDUFB11 TTPA TRNE AKT2 ABCC8 DMXL2 GTF2I CTRC TRNW COX3 POLR3A MTNR1B IL2RA LRAT PRKAR1A KCNJ11 HNF4A PRPH2 RNASEH2C LMNA CLRN1 TRNH OPA1 NPM1 ABCC8 HFE NRL PDE6A APOE GPR35 HNF4A AIRE TRNS2 MLXIPL GPD2 LMNA TTC8 SAMHD1 EDA TP53 NUBPL SNRPN TRMT10A NKX2-5 PWAR1 RPE65 PDX1 IGF2BP2 PRSS2 PRKACA AHI1 CAVIN1 PTCH1 BLK PPARG SPATA7 NPAP1 EIF2S3 BAZ1B SNRNP200 HNF4A POLA1 AHR NEUROD1 NDUFV2 PDX1 PSTPIP1 HJV AIP PALLD HLA-DQB1 TRNE TCF7L2 CTC1 NSMCE2 TTC7A NOP10 OTX2 PRSS2 PRKAR1A XRCC4 SOX3 HNF4A IMPDH1 NDUFB3 IFT140 DCAF17 KLF11 NEUROD1 FOXP1 CDON LIPC PLAGL1 CISD2 NDUFA1 PRSS1 GTF2IRD1 VANGL1 AGPAT2
HP:0001513: Obesity
Genes 469
MID2 LMNA PDE11A BBS10 HGSNAT ABCC8 GABRA3 RP1 ADRB2 AKT2 CXORF56 OFD1 APPL1 TRIP12 LAS1L CCDC141 CARTPT CHD7 MAK TACR3 FEZF1 IFT172 BEST1 XRCC4 FSCN2 GABRD PWRN1 ADCY3 CRX SETD5 BBS2 CRB1 FGF17 IGF1R HESX1 MTTP SLC25A4 CCDC141 SOX10 RP9 HCFC1 CTSH PDE4D LMNA USP9X CUL4B HDAC8 GNAS PDE4D SUFU TSPAN7 TBX1 PRPF4 TUB TUB RHO KISS1R MAPK8IP3 KMT2A PRMT7 SETD2 INS AIP VPS13B DNMT3A RAP1B SAG TRAPPC9 SIM1 MED12 SDCCAG8 CEP164 USH2A UFD1 PNKP PRPF6 LIPE PHIP IL1RAPL1 CNGA1 IFT74 FHL1 MERTK PHF6 PROK2 PDSS1 ARHGEF18 SH2B1 IDH3B FGFR3 PRPF3 SLC7A14 PAX4 JMJD1C DPYD MAN1B1 NR0B2 WT1 SNORD116-1 FMR1 IPW KCNJ18 NSD1 ATP6AP2 ACSL4 P2RY11 MC3R ALMS1 RAB23 PROK2 FGFR1 PCNT NTRK2 CTNNB1 STX16 DYRK1B HDAC8 SCAPER PRCD SEC24C PROKR2 SYNE1 SMC1A PCARE AKT2 TNFSF4 FGF8 DHDDS ALB ADRB3 SYNE2 MYT1L LEPR BBS12 ZNF513 NIN ADNP LEP ARMC5 IQSEC2 PPARG GUCA1B POMC BBIP1 THOC2 UPF3B PAK3 HACE1 SNORD115-1 BBS1 MOG SYP COMT GNAS-AS1 MKKS GNAS WNT4 SDCCAG8 ROM1 C8ORF37 PDE6B ZNF41 GHRL IFT172 GATA4 PDE6G ELN RAB23 AGTR2 TBX1 HS6ST1 RGR FGFR1 ACADVL EMD PTEN PROM1 PSMD12 SEMA4A ARL6 MEGF8 RAI1 ABCA4 MAGEL2 DMD ELN TULP1 DCC PAX6 UCP3 CUL4B REEP6 ZNF711 RREB1 SRY PDGFB DHX38 DEAF1 HDAC8 NPHP1 RP2 RLBP1 RNPC3 C8ORF37 GP1BB AGRP SETD2 RFC2 PHF6 MC4R FRMPD4 IGF1 USP8 EP300 HLA-DQB1 ARL3 IFT88 CEL ZNF81 OFD1 MKRN3-AS1 LAS1L BBS7 BBS2 RDH12 PRDM16 MKS1 HACE1 SMC3 IDH3A PIGT SHOX BBS9 IFT172 ARHGEF6 SKI CEP290 PRMT7 PDE4D CYP19A1 POMGNT1 KCNAB2 SIN3A H6PD KDM6A IFT27 LIMK1 TBL2 LZTFL1 BLK PNPLA6 USP8 ARL6 ARL2BP HLA-DRB1 IMPG2 XYLT1 BDNF ZBTB20 RBP3 POMC KIZ SH3KBP1 ARMC5 PRPF8 TOPORS BBS4 RERE AFF4 RPGR SLC9A7 SOX2 ALG13 HERC2 MRAP2 GNAS HUWE1 EIF2S3 TRAPPC9 POU3F4 FAM161A LEPR ARNT2 HIRA BBS9 GNAS DUSP6 MCM3AP RAI1 AFF4 MECP2 FOXP1 IQSEC2 BBS10 CEP19 SH2B1 SHANK3 RAD21 GDI1 BBS1 SMARCB1 SIM1 TRIM32 RAP1A WDR11 CLIP2 WT1 SPRY4 CACNA1S NIPBL NR2E3 MKKS KIF7 KIAA1549 GHR ANOS1 KLHL7 CNKSR2 CNGB1 HCRT GCK MC4R CEP290 EHMT1 AGBL5 TAF1 ZNF365 PROKR2 CA4 HNF1A BBS12 CLCN4 POMC MTFMT EYS NEK2 TMEM67 PCSK1 RPS6KA3 MAGEL2 CERKL GNAS EHMT1 ADNP MKS1 SDC3 FLII TTC8 MKRN3 BRAF NSMF TMEM43 MOG ENPP1 DLG3 CCDC28B BBS7 SLC10A7 SLC7A7 EXOC6B RBMX CDH23 IFT27 NDN SMAD4 IQSEC2 TRIM32 ZNF408 HESX1 TCF20 ATRX CANT1 GNAS EGF ALMS1 ARL6 GNAS FLRT3 BBS2 CDHR1 PRPF31 BBIP1 PRKAR1A IGFALS SEMA3A PAX6 PCNT ARVCF GTF2I FTSJ1 LRAT P4HTM PRKAR1A FTO ARL13B KCNJ11 PRPH2 APC2 IFT172 CLRN1 KMT2D LZTFL1 NRL PDE6A APOE TBX1 BBS4 INPP5E PCSK1 KIDINS220 PTCHD1 MLXIPL USP27X HDAC4 TBX3 MEGF8 TTC8 SNRPN TRAF3IP1 PWAR1 RPE65 ATRX PDX1 TBX3 TTC8 IL17RD POGZ ARX AHI1 MAN1B1 BLK CYP7A1 SPATA7 NPAP1 BBS5 EIF2S3 BAZ1B SNRNP200 AHR NEUROD1 WDPCP XYLT1 VPS13B BBS5 ZNF711 GNAS OTX2 ERMARD KIDINS220 SOX3 HNF4A IMPDH1 IFT140 KLF11 RAB39B BPTF HSD11B1 SPG11 RPS6KA3 NF2 MECP2 LEP WDR34 UBE3A CNNM2 C8ORF37 GTF2IRD1 CREBBP SH2B1
Protein Mutations 3
G20210A P12A W64R
HP:0001824: Weight loss
Genes 325
TRNF SCNN1B WT1 EPAS1 SCNN1A GABRA3 TRAIP COL1A1 PTEN MLX LIPA TCF4 STAT3 INSR LPIN2 HAVCR2 KLRC4 MC2R NPM1 JPH3 KIF1B H19 NOD2 PLAGL1 IL6 MECP2 IL12A WT1 TRNL1 POLG PRKAR1A BCL10 MRAP FOXP3 FIP1L1 KCNJ11 SDHD UBE2T INS CNTNAP1 KIF1B DAXX MST1 PML MALT1 VHL TBL1XR1 IL12A-AS1 TSHR PRNP CDH23 ERAP1 RPS20 MDH2 FLI1 BMPR1A CUL4B TP53 GJB3 FOXP1 TRIM28 B2M ND1 FANCL PDX1 SDHA ATP7B SCNN1G RHBDF2 RBBP8 MPL AKT1 NAB2 JAK2 ERCC5 WT1 COX2 EDN3 TP53 BCL2 JPH3 STAT6 TYMP EIF2AK3 KRAS PALB2 SNCA SEMA4A SDHC LRRK2 BRIP1 DCTN1 ACADM CACNA1S NBN FANCF IGH RET XRCC2 COL6A2 PRNP TSHR BRCA2 IGH HLA-B TRNQ NDP EDNRB UNC80 HLA-DPB1 DLST VPS35 PALB2 HSPG2 MLH1 TRIM37 TMEM127 STAR MEFV KCNJ18 FANCE C4A BMPR1A UBAC2 SDHD CALR PTPN22 KDSR POLG HLA-DRB1 KCNJ11 TRNS1 ERCC2 PTEN TRIP13 PLK4 TP53 RAD51 TTR EWSR1 IL23R PMS1 GIGYF2 F5 STAT3 ATR CHEK2 DNAJC13 BTK HYMAI FANCA MSH6 KRT1 POU6F2 HTT SLC9A6 PLA2G6 SUCLA2 FANCD2 TET2 SLC6A8 GJA1 ATRX PIK3CA PRNP KRT10 FANCM RET VHL CFTR SLC52A2 SDHAF1 SDHB SLC25A11 TLR4 BIRC3 ERCC4 SDHB GCK EPCAM IRF2BP2 LMNA KCNJ18 PIK3R1 HLA-DPA1 KRAS GDNF ACAT1 STAT4 SDHAF2 LRP12 SDHB DIS3L2 IL10 ATM COL5A2 IGH RB1 NNT NALCN PMS2 CYP24A1 BCOR SMAD4 ERCC3 BRCA2 ERCC4 TRIM28 PCNT SDHC BRCA2 RAD51C HLA-B JAK2 VPS13A SLC39A4 SDHD GBA SEMA3D AK2 TRNW COX3 RRM2B TGFBR2 HMGCL POLG UNC80 BRCA1 TYMP GATA4 COL5A1 RFWD3 SNCA BTNL2 SLX4 TRNH COX1 FH IKZF1 NOD2 GATA2 JAK2 REST ZBTB16 ABCC8 NUMA1 GPR35 TXNRD2 ND5 MAFB ND4 SLC11A1 BCL6 CENPJ TRNS2 COL12A1 HMBS PTPN22 FANCG STAT5B FANCI TP53 TGFB1 CENPE SEMA3C CEP152 AVP ABCC8 MPL RRM2B FAN1 FANCC CDC73 IL12B MAX ERCC4 FAS HLA-DRB1 CCR1 MAD2L2 FANCB TRPV4 GJB4 PALLD HLA-DRB1 HLA-DQB1 SLC52A3 EIF4G1 ATRIP PTEN CCND1 HLA-DRB1 RNF168 GPC3 NABP1 SDHB MSH2 ECE1 COL6A1 IFNGR1 JAK2 COL6A3 RET SDHA NRTN PANK2 CDKN2A GALT CACNA1S MLH3 ND6 CTLA4 PRTN3 RARA HLCS CCND1 TET2 ZFP57 HLA-B BRCA1 MPL THPO GNPTAB DCTN1 SDHD
Protein Mutations 2
I148M P12A