SNPMiner Trials by Shray Alag

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SNPMiner SNPMiner Trials (Home Page)


Report for Mutation C3435T

Developed by Shray Alag, 2020-2021.
SNP Clinical Trial Gene

There are 16 clinical trials

Clinical Trials


1 Conversion Pharmacodynamic Study in Stable Renal Transplant Patients Receiving Tacrolimus Two Times a Day to a New Formulation of Tacrolimus - LCP Tacro - 1 Time a Day.

LCP-Tacro is an extended-release formulation of tacrolimus designed for once-daily dosing. Phase 1 studies demonstrated greater bioavailability than twice-daily tacrolimus capsules and no new safety concerns. - Stable kidney transplant patients can be safely converted from Adoport® twice-daily to LCP-Tacro®. - The greater bioavailability of LCP-Tacro after once-daily dosing results in similar (AUC) exposure, at a dose approximately 30% less, than the total daily dose of Adoport®. - LCP-Tacro provides a slow drug release and this results in flatter kinetics characterized by significantly lower peak-trough fluctuations. - CN is the major cellular target of the calcineurin inhibitors (CNIs) cyclosporine A (CsA) and tacrolimus. The ability of these drugs to inhibit CN activity is dependent on their binding to the respective immunophilins, cyclophilins A and B for CsA and FKBP12 for tacrolimus. - CN inhibition is a rate limiting phenomenon. Over concentrations of tacrolimus does not correlate with an increase in the CN activity.

NCT02961608
Conditions
  1. Kidney Transplant; Complications
Interventions
  1. Drug: Drug conversion from Tacrolimus (Prograf® or Adoport®) to LCP-Tacrolimus (Envarsus®)

Set TAC trough concentrations for optimal inhibition of CN.. drug exposure according to CYP3A (CYP3A4 and CYP3A5 * 22 * 3) and ABCB1 (C3435T) polymorphism.. Analysis of drug exposure according to CYP3A (CYP3A4 and CYP3A5 * 22 * 3) and ABCB1 (C3435T) polymorphism.. Inclusion Criteria: - Adult patients (≥ 18 years). --- C3435T ---

Set TAC trough concentrations for optimal inhibition of CN.. drug exposure according to CYP3A (CYP3A4 and CYP3A5 * 22 * 3) and ABCB1 (C3435T) polymorphism.. Analysis of drug exposure according to CYP3A (CYP3A4 and CYP3A5 * 22 * 3) and ABCB1 (C3435T) polymorphism.. Inclusion Criteria: - Adult patients (≥ 18 years). --- C3435T --- --- C3435T ---

Primary Outcomes

Description: The main objective of this study is to compare the area under the curve (AUC) of CN activity after administration of a sustained release formulation (LCP- Tacro, Envarsus®) compared to an immediate release formulation (Prograf®) of TAC in renal transplant patients.

Measure: Area under the curve (AUC) of CN activity

Time: Baseline and 35 days post conversion

Secondary Outcomes

Description: Pharmacokinetic study AUC 0-24 h of each TAC formulation 12h (Prograf®) and the new formulation of TAC every 24h (LCP- Tacro, Envarsus®).

Measure: Area Under the curve 0-24 h of each TAC formulation

Time: Baseline and 35 days post conversion

Description: Study PK / PD: relationship PK TAC (drug exposure) and PD (activity CN) of both formulations. Set TAC trough concentrations for optimal inhibition of CN.

Measure: TAC trough concentrations for optimal inhibition of CN

Time: Baseline and 35 days post conversion

Description: Analysis of drug exposure according to CYP3A (CYP3A4 and CYP3A5 * 22 * 3) and ABCB1 (C3435T) polymorphism.

Measure: drug exposure according to CYP3A (CYP3A4 and CYP3A5 * 22 * 3) and ABCB1 (C3435T) polymorphism.

Time: Baseline and 35 days post conversion

2 Prospective Study of the Influence of CYP3A4/CYP3A5 and MDR1 Gene Single Nucleotide Polymorphisms on Long-Term Tacrolimus Disposition in Renal Allograft Recipients: a Five Year Follow-up Study Using Abbreviated Concentration-Time Measurements.

An evaluation of the effects of genetically determined variant metabolizing and transporting proteins involved in the disposition of the immunosuppressive drug tacrolimus in renal transplant recipients. In a five year follow-up study tacrolimus dose-corrected exposure changes significantly and the effect(s) of single nucleotide polymorphisms of the CYP3A4/CYP3A5 and MDR1 genes on the latter is assessed in this study.

NCT00411944
Conditions
  1. Renal Transplantation

The effects of the CYP3A5*1, CYP3A4*1B, MDR1 G2677T/A and C3435T single nucleotide polymorphisms on the evolution of tacrolimus disposition are studied over 5 years in order to clarify the interrelationship between CYP3A5, CYP3A4 and MDR1 genotypes, time-dependent exposure and tacrolimus-related toxicity. --- G2677T --- --- C3435T ---


3 A Controlled, Randomized, Parallel, Multicentre Study to Assess Safety and Tolerability of the Oral Direct Thrombin Inhibitor AZD0837, Given as an Extended-release Formulation, in the Prevention of Stroke and Systemic Embolic Events in Patients With Atrial Fibrillation

The main purpose of this study is to provide dose-guiding information by assessing the safety and tolerability of 4 different dosing regimens of an extended-release (ER) formulation of AZD0837 compared with well-controlled, dose-adjusted Vitamin-K antagonists (VKA) (aiming for an international normalized ratio (INR) 2.0 to 3.0) in patients with non-valvular atrial fibrillation (AF) with one or more additional risk factors for stroke.

NCT00684307
Conditions
  1. Nonvalvular Atrial Fibrillation
Interventions
  1. Drug: AZD0837
  2. Drug: Vitamin-K antagonist at INR 2-3
  3. Drug: AZD0837
MeSH:Atrial Fibrillation
HPO:Atrial fibrillation Paroxysmal atrial fibrillation

Oral Clearance (CL/F) of AR-H067637XX (Active Metabolite) for C3435T Genotype TT. --- C3435T ---

Oral clearance of AR-H067637XX in subgroup of patients with genotype TT for gene polymorphism ABCB1 C3435T. --- C3435T ---

Oral Clearance (CL/F) of AR-H067637XX (Active Metabolite) for C3435T Genotype TC. --- C3435T ---

Oral clearance of AR-H067637XX in subgroup of patients with genotype TC for gene polymorphism ABCB1 C3435T. --- C3435T ---

Oral Clearance (CL/F) of AR-H067637XX (Active Metabolite) for C3435T Genotype CC. --- C3435T ---

Oral clearance of AR-H067637XX in subgroup of patients with genotype CC for gene polymorphism ABCB1 C3435T. --- C3435T ---

Primary Outcomes

Description: Number of patients with a bleeding event while on study drug. Patients with multiple events are counted once

Measure: Bleeding Events

Time: 36 weeks according to protocol. For patients who discontinued treatment the time frame was <36 weeks. Mean number of weeks was 21 weeks (baseline to end of treatment visit)

Description: Change in Creatinine values from baseline to week 12 visit for patients while on study drug (week 12 visit-baseline)

Measure: Creatinine

Time: 12 weeks according to protocol.(baseline to week 12 visit)

Description: Number of patients while on study drug with ALAT>=3 times upper limit of normal.l

Measure: Alanine Aminotransferase (ALAT)

Time: 36 weeks according to protocol. For patients who discontinued treatment the time frame was <36 weeks. Mean number of weeks was 21 weeks (baseline to end of treatment visit)

Description: Number of patients while on study drug with Bilirubin>=2 times upper limit of normal

Measure: Bilirubin

Time: 36 weeks according to protocol. For patients who discontinued treatment the time frame was <36 weeks. Mean number of weeks was 21 weeks (baseline to end of treatment visit)

Secondary Outcomes

Description: Change in D-Dimer values from enrolment to week 12 visit for VKA naïve patients while on study drug (week 12 visit-enrolment)

Measure: D-Dimer

Time: 14 weeks according to protocol.(enrolment to week 12 visit)

Description: Change in Activated partial thromboplastin time (APTT) from baseline to week 12 visit for VKA naïve patients while on study drug (week 12 visit-baseline)

Measure: Activated Partial Thromboplastin Time (APTT)

Time: 12 weeks according to protocol.(baseline to week 12 visit)

Description: Change in Ecarin clotting time (ECT) from baseline to week 12 visit for patients while on study drug (week 12 visit-baseline)

Measure: Ecarin Clotting Time (ECT)

Time: 12 weeks according to protocol.(baseline to week 12 visit)

Description: Assessment made on the week 12 visit

Measure: Plasma Concentration of AZD0837 (Prodrug)

Time: 12 weeks after baseline according to protocol

Description: Assessment made on the week 12 visit

Measure: Plasma Concentration of AR-H067637XX (Active Metabolite)

Time: 12 weeks after baseline according to protocol

Description: Oral clearance of AR-H067637XX in subgroup of patients with genotype TT for gene polymorphism ABCB1 C3435T

Measure: Oral Clearance (CL/F) of AR-H067637XX (Active Metabolite) for C3435T Genotype TT

Time: 36 weeks according to protocol

Description: Oral clearance of AR-H067637XX in subgroup of patients with genotype TC for gene polymorphism ABCB1 C3435T

Measure: Oral Clearance (CL/F) of AR-H067637XX (Active Metabolite) for C3435T Genotype TC

Time: 36 weeks according to protocol

Description: Oral clearance of AR-H067637XX in subgroup of patients with genotype CC for gene polymorphism ABCB1 C3435T

Measure: Oral Clearance (CL/F) of AR-H067637XX (Active Metabolite) for C3435T Genotype CC

Time: 36 weeks according to protocol

4 The Pharmacogenetics of Oxycodone Analgesia in Human Experimental Pain Models

Thirty-two healthy volunteers will be submitted to experimental pain and on the 2 study days receive Oxycodone 20 mg po vs. placebo. Half of the volunteers will be poor metabolizers according to CYP2D6 genotype and half will be extensive metabolizers (EM) and have an enzyme with normal function. The study hypothesis is that PM will experience less pain relief than EM.

NCT00271973
Conditions
  1. Healthy
Interventions
  1. Drug: Oxycodone

Among these are the A118G SNP in the μ-receptor gene OPRM1 and the C3435T and G2677T/A SNPs in the MDR-1 gene of P-glycoprotein. --- A118G --- --- C3435T ---

Primary Outcomes

Measure: Pain threshold and tolerance measured by electrical stimulation and pain intensity measured by cold pressor test.

Secondary Outcomes

Measure: The above compared to SNPs. Plasma levels of oxycodone and metabolites.

5 The Pharmacogenetics of Oxycodone Analgesia in Postoperative Pain

Patients undergoing surgery (thyroidectomy and hysterectomy) will postoperatively receive oxycodone intravenously (IV) as pain management with morphine as an escape medicine, if there is insufficient pain relief with oxycodone. Patients' pain and side effects will be registered and after 24 hours they will answer a questionnaire. All included patients will be genotyped accordingly to CYP2D6 and relevant single nucleotide polymorphisms (SNPs), and measures of plasma levels of oxycodone will be performed.

NCT00260260
Conditions
  1. Postoperative Pain
Interventions
  1. Drug: Oxycodone
MeSH:Pain, Postoperative

Among these are the A118G SNP in the μ-receptor gene OPRM1 and the C3435T and G2677T/A SNPs in the MDR-1 gene of P-glycoprotein. --- A118G --- --- C3435T ---

Primary Outcomes

Measure: Responder (satisfaction with pain treatment in questionnaire and no escape medication)

Measure: Non-responder (dissatisfaction with pain management in questionnaire and/or escape medication)

Measure: Responder status compared to CYP2D6 genotype

Secondary Outcomes

Measure: Registration of pain, side effects and total amount of oxycodone given compared to CYP2D6 genotype and SNPs

6 Federal Cardiomonitoring System. Determination of the Efficiency of a Single-lead ECG Recorded With CardioQVARK Cardiac Monitor in Order to Detect Atrial Fibrillation in Primary Health Centers.

This interventional prospective multicenter nonrandomized clinical and epidemiological study is the first Russian study aimed at evaluating the effectiveness of a single-lead electrocardiography device (CardioQVARK) in screening for atrial fibrillation in primary health care.

NCT04204330
Conditions
  1. Atrial Fibrillation
Interventions
  1. Device: CardioQvark cardiac monitor and software, single-lead ECG
MeSH:Atrial Fibrillation
HPO:Atrial fibrillation Paroxysmal atrial fibrillation

For new oral anticoagulants - rs2244613 of the gene CES1, rs1045642 (C3435T), rs1128503 (C1236T), rs2032582 (G2677T / А) of the gene ABCB1, rs2231142 (С421А, Q141K) of the gene ABCG2, rs776746 (A6986G * 399 CYP3 CYP3) CYP3A4.. Inclusion Criteria: Men and women aged 18 to 96 years who have one or more of the following risk factors: - hypertonic disease - history of ischemic stroke or transient ischemic attacks - type 1 and type 2 diabetes - 1-3 degrees obesity - heart failure or the presence of a clinic to reduce exercise tolerance associated with shortness of breath - coronary heart disease or the presence of symptoms of chest pain, in the absence of an established diagnosis of coronary heart disease - the presence of peripheral arterial atherosclerosis - the presence of a clinic of interruptions in the work of the heart (bouts of rapid, irregular heartbeats, pauses in work of heart) Non-inclusion criteria: - Acute coronary syndrome - Acute ischemic or hemorrhagic stroke - Acute psychosis - The presence of severe concomitant diseases with an expected life expectancy of less than 2 years Exclusion Criteria: Refusal of further participation in the study Inclusion Criteria: Men and women aged 18 to 96 years who have one or more of the following risk factors: - hypertonic disease - history of ischemic stroke or transient ischemic attacks - type 1 and type 2 diabetes - 1-3 degrees obesity - heart failure or the presence of a clinic to reduce exercise tolerance associated with shortness of breath - coronary heart disease or the presence of symptoms of chest pain, in the absence of an established diagnosis of coronary heart disease - the presence of peripheral arterial atherosclerosis - the presence of a clinic of interruptions in the work of the heart (bouts of rapid, irregular heartbeats, pauses in work of heart) Non-inclusion criteria: - Acute coronary syndrome - Acute ischemic or hemorrhagic stroke - Acute psychosis - The presence of severe concomitant diseases with an expected life expectancy of less than 2 years Exclusion Criteria: Refusal of further participation in the study Atrial Fibrillation Atrial Fibrillation This is an interventional, prospective, multicenter, nonrandomized clinical and epidemiological study. --- C3435T ---

Primary Outcomes

Description: Total number of AF cases newly diagnosed during the study period.

Measure: Total number of AF cases newly diagnosed during the study period.

Time: Through study completion, an average of 1 year

Description: Number of patients who, for the first time ever, were assigned to anticoagulation therapy.

Measure: Number of patients who, for the first time ever, were assigned to anticoagulation therapy.

Time: Through study completion, an average of 1 year

Description: Assessed using data obtained from pharmacokinetic analysis. International normalised ratio (INR) - target range from 2 to 3.

Measure: Compliance to anticoagulation therapy for warfarin.

Time: 6 months after administration of anticoagulants

Description: Assessed using data obtained from pharmacokinetic analysis. Quantitative determination of the concentration of drugs in the blood (blood sampling three hours after taking the drug).

Measure: Compliance to anticoagulation therapy for new oral anticoagulants.

Time: 6 months after administration of anticoagulants

Description: Evaluated as incremental cost-effectiveness ratio of screening per quality adjusted life year gained, and per stroke avoided.

Measure: Cost-effectiveness of using the single-lead CardioQVARK ECG device in screening for AF in primary health care.

Time: Through study completion, an average of 1 year

Secondary Outcomes

Description: Mean time to diagnosis.

Measure: Mean time to diagnosis.

Time: Through study completion, an average of 1 year

Description: Number of patients with a CHA₂DS₂-VASc score (the CHA2DS2-VASc Score is the most commonly utilized method to predict thromboembolic risk in atrial fibrillation) of ≥ 1.

Measure: Number of patients with a CHA₂DS₂-VASc score (the CHA2DS2-VASc Score is the most commonly utilized method to predict thromboembolic risk in atrial fibrillation) of ≥ 1.

Time: Through study completion, an average of 1 year

Description: Number of patients with a CHA₂DS₂-VASc score (the CHA2DS2-VASc Score is the most commonly utilized method to predict thromboembolic risk in atrial fibrillation) of ≥ 2.

Measure: Number of patients with a CHA₂DS₂-VASc score (the CHA2DS2-VASc Score is the most commonly utilized method to predict thromboembolic risk in atrial fibrillation) of ≥ 2.

Time: Through study completion, an average of 1 year

Description: Defined as frequency of ischemic stroke or transient ischemic attack in patients with newly diagnosed AF and assigned anticoagulants.

Measure: Incidence of ischemic stroke or transient ischemic attack after enrollment in the study.

Time: Through study completion, an average of 1 year

Description: Defined as frequency of massive hemorrhage in patients with newly diagnosed AF and assigned anticoagulants.

Measure: Incidence of massive hemorrhage after enrollment in the study.

Time: Through study completion, an average of 1 year

Description: Defined as frequency of hemorrhagic stroke in patients with newly diagnosed AF and assigned anticoagulants.

Measure: Incidence of hemorrhagic stroke after enrollment in the study.

Time: Through study completion, an average of 1 year

Description: For warfarin - CYP2C9 (CYP2C9 * 2, CYP2C9 * 3), VKORC1 (1 marker), CYP4F2 (1 marker), GGCX (1 marker). For new oral anticoagulants - rs2244613 of the gene CES1, rs1045642 (C3435T), rs1128503 (C1236T), rs2032582 (G2677T / А) of the gene ABCB1, rs2231142 (С421А, Q141K) of the gene ABCG2, rs776746 (A6986G * 399 CYP3 CYP3) CYP3A4.

Measure: Pharmacogenetic testing by polymorphic markers

Time: 6 months after administration of anticoagulants

7 Influence of Body Size and Composition on Response to Hydromorphone in ED Patients With Acute Pain

Pain is the most common complaint for patients presenting to the emergency department (ED). Inadequate pain relief is also a common problem in ED. Patients' pain perceptions and responses to intravenous opioids vary widely and are influenced by multiple factors. The objective of the current study is to examine the association between total body weight, BMI (body mass index) and clinical response to a fixed dose of intravenous hydromorphone.

NCT01675778
Conditions
  1. Pain
Interventions
  1. Drug: Hydromorphone
MeSH:Acute Pain

The reported value represents the correlation coefficient.. Effects of Single-nucleotide Polymorphisms of Opioid Transporter (ABCB1, C3435T) on the Correlation Between TBW and Change in Pain Intensity. --- C3435T ---

Clinical responses to hydromorphone could be affected by the single-nucleotide polymorphisms (SNPs) in gene involving opioid transporter (ABCB1, C3435T). --- C3435T ---

Primary Outcomes

Description: Participants were asked to rate their pain levels from 0 (=no pain) to 10 (= worst pain). The change in pain intensity was determined by subtracting the intensity reported before treatment from the intensity reported 30 minutes after treatment. Pearson correlation was used to assess the correlation between change in pain intensity and total body weight (TBW). The reported value represents the correlation coefficient.

Measure: Correlation Between Change in Pain Intensity and TBW at 30 Minutes Post-treatment

Time: 30 minutes post-treatment

Description: Participants were asked to rate their pain levels from 0 (=no pain) to 10 (= worst pain). The change in pain intensity was determined by subtracting the intensity reported before treatment from the intensity reported 30 minutes after treatment. Pearson correlation was used to assess the correlation between change in pain intensity and body mass index (BMI). The reported value represents the correlation coefficient.

Measure: Correlation Between Change in Pain Intensity and BMI at 30 Minutes Post-treatment

Time: 30 minutes post-treatment

Secondary Outcomes

Description: Participants were asked to rate their pain levels from 0 (=no pain) to 10 (= worst pain). The change in pain intensity was determined by subtracting the intensity reported before treatment from the intensity reported 15 minutes after treatment. Pearson correlation was used to assess the correlation between change in pain intensity and total body weight (TBW). The reported value represents the correlation coefficient.

Measure: Correlation Between Change in Pain Intensity and TBW at 15 Minutes Post-treatment

Time: 15 minutes post-treatment

Description: Participant's satisfaction with their treatment were assessed by self-report. After treatment, participants were asked "How satisfied are you with the result of your pain treatment today?" and they were told to pick their satisfaction level from "very dissatisfied," "dissatisfied," "uncertain," "satisfied," and "very satisfied." Participants at each level is reported.

Measure: Pain Treatment Satisfaction Levels as Assessed by Self-report

Time: 30 minutes post-treatment

Description: Opioids can induce respiratory depression, which could lead to low oxygen saturation level. Prolonged low oxygen saturation level < 92% could cause brain damage. Understanding all potential negative impacts of Hydromorphone helps make it safer for clinical use.

Measure: Number of Participants With Oxygen Saturation Level < 92%

Time: 30 minutes post-treatment

Description: Opioids can could induce nausea. Number of participants with nausea is reported. Understanding all potential negative impacts of Hydromorphone helps make it safer for clinical use.

Measure: Number of Participants With Nausea

Time: 30 minutes post-treatment

Description: This study evaluated the effect of gender on the correlation between Total Body Weight (TBW) and change in pain intensity. Participants were asked to rate their pain levels from o (=no pain) to 10 (= worst pain). The change in pain intensity was determined by subtracting the intensity reported before treatment from the intensity reported after treatment. Pearson correlation was used to assess the correlation between change in pain intensity and total body weight (TBW). The reported value represents the correlation coefficient.

Measure: Effect of Gender on the Correlation Between TBW and Change in Pain Intensity

Time: 30 minutes post-treatment

Description: This study evaluated the effect of race/ethnicity on the correlation between total body weight (TBW) and change in pain intensity. Participants were asked to rate their pain levels from o (=no pain) to 10 (= worst pain). The change in pain intensity was determined by subtracting the intensity reported before treatment from the intensity reported after treatment. Pearson correlation was used to assess the correlation between change in pain intensity and total body weight (TBW). The reported value represents the correlation coefficient.

Measure: Effects of Race/Ethnicity on the Correlation Between TBW and Change in Pain Intensity

Time: 30 minutes post-treatment

Description: This study evaluated the effect of genetic factors on the correlation between Total Body Weight (TBW) and change in pain intensity. Clinical responses to hydromorphone could be affected by the single-nucleotide polymorphisms (SNPs) in gene involving opioid receptor (OPRM1, A118G). Participants were asked to rate their pain levels from 0 (=no pain) to 10 (= worst pain). The change in pain intensity was determined by subtracting the intensity reported before treatment from the intensity reported after treatment. The median and inter-quantile ranges of pain intensity reduction post-treatment were compared among patients by Kruskal-Wallis test.

Measure: Effects of Single-nucleotide Polymorphisms of Opioid Receptor (OPRM1, A118G) on the Correlation Between TBW and Change in Pain Intensity

Time: 30 minutes post-treatment

Description: Age might affect the responses to the hydromorphone treatment. The effects of age on the correlation between total body weight (TBW) and change in pain intensity. The mean of age was compared in TBW tertile groups.

Measure: Effects of Age on the Correlation Between TBW and Change in Pain Intensity

Time: 30 minutes post-treatment

Description: Opioids can induce low blood pressure. Prolonged low systolic blood pressure < 90 mmHg can cause shock and multi-organ failure. Understanding all potential negative impacts of Hydromorphone helps make it safer for clinical use.

Measure: Number of Participant With Systolic Blood Pressure < 90 mmHg

Time: 30 minutes post-treatment

Description: This study evaluated the effect of gender on the correlation between body mass index (BMI) and change in pain intensity. Participants were asked to rate their pain levels from 0 (=no pain) to 10 (= worst pain). The change in pain intensity was determined by subtracting the intensity reported before treatment from the intensity reported after treatment. Pearson correlation was used to assess the correlation between change in pain intensity and body mass index (BMI). The reported value represents the correlation coefficient.

Measure: Effect of Gender on the Correlation Between BMI and Change in Pain Intensity

Time: 30 minutes post-treatment

Description: Opioids can induce vomit. Number of participants with vomit is reported. Understanding all potential negative impacts of Hydromorphone helps make it safer for clinical use.

Measure: Number of Participants With Vomit

Time: 30 minutes post-treatment

Description: Opioids can induce skin itching. Number of participants with skin itching is reported. Understanding all potential negative impacts of Hydromorphone helps make it safer for clinical use.

Measure: Number of Participants With Skin Itching

Time: 30 minutes post-treatment

Description: Participants were asked to rate their pain levels from 0 (=no pain) to 10 (= worst pain). The change in pain intensity was determined by subtracting the intensity reported before treatment from the intensity reported 15 minutes after treatment. Pearson correlation was used to assess the correlation between change in pain intensity and body mass index (BMI). The reported value represents the correlation coefficient.

Measure: Association Between Change in Pain Intensity and BMI at 15 Minutes Post-treatment

Time: 15 minutes post-treatment

Description: This study evaluated the effect of genetic factors on the correlation between Total Body Weight (TBW) and change in pain intensity. Clinical responses to hydromorphone could be affected by the single-nucleotide polymorphisms (SNPs) in gene involving opioid transporter (ABCB1, C3435T). Participants were asked to rate their pain levels from 0 (=no pain) to 10 (= worst pain). The change in pain intensity was determined by subtracting the intensity reported before treatment from the intensity reported after treatment. The mean and inter-quantile ranges of pain intensity reduction post-treatment were compared among patients by Kruskal-Wallis test.

Measure: Effects of Single-nucleotide Polymorphisms of Opioid Transporter (ABCB1, C3435T) on the Correlation Between TBW and Change in Pain Intensity

Time: 30 minutes post-treatment

Description: This study evaluated the effect of genetic factors on the correlation between Total Body Weight (TBW) and change in pain intensity. Clinical responses to hydromorphone could be affected by the single-nucleotide polymorphisms (SNPs) in gene involving pain sensitivity (COMT, G1947A). Participants were asked to rate their pain levels from 0 (=no pain) to 10 (= worst pain). The change in pain intensity was determined by subtracting the intensity reported before treatment from the intensity reported after treatment. The mean and inter-quantile ranges of pain intensity reduction post-treatment were compared among patients by Kruskal-Wallis test.

Measure: Effects of Single-nucleotide Polymorphisms of Pain Sensitivity (COMT, G1947A) on the Correlation Between TBW and Change in Pain Intensity

Time: 30 minutes post-treatment

Description: This study evaluated the effect of genetic factors on the correlation between Total Body Weight (TBW) and change in pain intensity. Clinical responses to hydromorphone could be affected by the single-nucleotide polymorphisms (SNPs) in gene involving opioid metabolism (UGT2B7, -G840A). Participants were asked to rate their pain levels from 0 (=no pain) to 10 (= worst pain). The change in pain intensity was determined by subtracting the intensity reported before treatment from the intensity reported after treatment. The mean and inter-quantile ranges of pain intensity reduction post-treatment were compared among patients by Kruskal-Wallis test.

Measure: Effects of Single-nucleotide Polymorphisms of Opioid Metabolism (UGT2B7, -G840A) on the Correlation Between TBW and Change in Pain Intensity

Time: 30 minutes post-treatment

Other Outcomes

Description: Some participants liked to receive additional analgesics after hydromorphone treatment. Number of participants who desired for additional analgesics is reported.

Measure: Number of Participants Who Desired for More Analgesics

Time: 30 minutes post-treatment

8 Influence of MDR1 Genotype on Indinavir and Saquinavir Pharmacokinetics in Healthy Volunteers

This study will examine whether a particular type of gene (MDR1) in the body can affect blood levels of two protease inhibitors, indinavir and saquinavir, which are used to treat people with HIV. If blood levels of these drugs are too low or too high, they may not work well or may cause side effects in patients. This study will determine how MDR1 genes might affect absorption of these medicines. Healthy normal volunteers between 18 and 50 years of age may be eligible for this study. Candidates will be screened with a medical history and blood and urine tests. The blood will be tested for: - Routine laboratory values for assessing general health - HIV - MDR1 gene type - Amount of P-glycoprotein (a protein made by the MDR1 gene) on T cells. Participants will have blood drawn three more times, as follows: - After one dose of the sedative midazolam (Versed(Registered Trademark)): Participants will take an 8-milligram dose of midazolam syrup by mouth. Four hours later, a single blood sample will be drawn through a needle in an arm vein. This part of the study will assess the efficiency of a certain enzyme involved in metabolizing (breaking down) indinavir and saquinavir. - After four doses of indinavir: About a week after taking the midazolam, participants will take 800 mg of indinavir (two capsules) 3 times a day (every 8 hours) for 1 day. The following morning they will come to the clinic, where a catheter (flexible plastic tube) will be placed in an arm vein for repeated blood draws. A blood sample will be drawn, and a fourth and final dose of indinavir will be given. Seven blood samples of about a teaspoon each will then be collected through the catheter over an 8-hour period to measure blood levels of the drug. - After 10 doses of saquinavir: About a week after the last dose of indinavir, participants will start taking 1,200 mg (6 capsules) of saquinavir soft-gelatin capsules 3 times a day for 3 days. On the fourth day, participants will come to the clinic. A catheter will be inserted into an arm vein and about 4 teaspoons of blood will be collected for routine laboratory tests and to measure saquinavir levels. A urine sample will also be collected for routine tests. Participants will then receive the tenth and final dose of saquinavir, and eight blood samples of about a teaspoon each will be collected through the catheter over an 8-hour period.

NCT00050180
Conditions
  1. Healthy
  2. HIV Infections
Interventions
  1. Drug: Midazolam
  2. Drug: Indinavir
  3. Drug: Saquinavir
MeSH:HIV Infections

Healthy HIV Infections HIV Infections The expression of P-glycoprotein, a transporter protein present in enterocytes as well as other cells involved in the absorption and distribution of HIV protease inhibitors, has been linked to a single nucleotide polymorphism (SNP) in exon 26 of the MDR1 gene, C3435T. --- C3435T ---


9 A Prospective Pilot Study to Evaluate the Effect of Systemic Adjuvant Therapy on the Cognitive and Brain Function of Breast Cancer Patients

The purpose of the study is to examine cognitive and brain function in stage I-III breast cancer patients who have undergone adjuvant systemic therapy (chemotherapy or chemotherapy plus anti-hormonal therapy) in comparison to a group of healthy controls. Our hypothesis is that systemic adjuvant therapy in the form of chemotherapy or chemotherapy and anti-hormonal therapy given to primary breast cancer patients can cause cognitive impairment. We hypothesize that the use of simultaneous PET/MRI will allow us to determine key regions in the brain that show metabolic, structural, and functional deficits in a semi-quantitative manner and reveal subtle changes that are often missed during neuropsychological tests due to the low sensitivity of neuropsychological batteries.

NCT02078531
Conditions
  1. Breast Cancer
MeSH:Breast Neoplasms
HPO:Breast carcinoma Neoplasm of the breast

For example, several genetic polymorphisms of multidrug resistance 1 (MDR1) have been identified that may influence P-glycoprotein (P-gp) function, one of the most studied polymorphisms being C3435T in exon26.P-gp which is present in the blood brain barrier affects the amount of drug uptake into the brain by actively transporting them out of the cells. --- C3435T ---

Primary Outcomes

Description: We hope to gain a better understanding of the complex and currently poorly understood relationship between chemotherapy/anti-hormonal therapy and possible cognitive decline in patients undergoing such therapy. In current practice, a large number of patients with primary breast cancer are offered adjuvant chemotherapy after surgery, followed by hormonal therapy in patients whose tumours are hormone receptor-positive. The management of many adverse effects of chemotherapy, such as nausea, vomiting and febrile neutropenia has improved, and concern has shifted to more subtle and potentially chronic problems such as cognitive dysfunction, which may affect patients' quality of life.

Measure: Change the relationship between chemotherapy/anti-hormonal therapy and possible cognitive decline in patients undergoing such therapy

Time: 1 year

10 Role of Genetic Factors in the Response to Digoxin in the Acute Treatment of Atrial Fibrillation

This study tested the hypothesis that response to digoxin is modulated by single Nucleotid Polymorphism (SNP): - Multi Drug Resistance (MDR1) gene haplotypes and Solute carrier organic anion transporter family member 1B3 (SLCO1B3) gene Polymorphism and their role in the response to treatement. - Aldosterone synthase (CYP11B2) gene and sodium channel, voltage-gated, type V alpha subunit gene (SCN5A) correlated with atrial fibrillation and their roles in response to digoxin.

NCT02167165
Conditions
  1. Atrial Fibrillation
Interventions
  1. Drug: Digoxin Injection
MeSH:Atrial Fibrillation
HPO:Atrial fibrillation Paroxysmal atrial fibrillation

The aim of the current study is to analyze the ABCB1: C1236T (Gly412Gly), G2677>T⁄A (Ala893Ser/ Thr) and C3435T (Il1145Ile) polymorphisms. --- C1236T --- --- Ala893Ser --- --- C3435T ---

Primary Outcomes

Description: In the current study we aimed at outlining the different MDR-1, SLCO1B3, CYP11B12 and SCN5A genotypes in a sample of Tunisian patients, suffering from AF and taking digoxin, to assess the role of SNPs in affecting serum digoxin concentrations, and studying the consequences on patients' clinical outcome. Patients will be monitored for 24 hours in an intensive care unit;

Measure: Correlation between the response to digoxin and the genotypes of the patients

Time: 24 hours

Secondary Outcomes

Description: Rhythm control: rate and delay of return to sinusal rhythm. Rate control: reduction of heart rate : HR <100 bpm or 20% reduction from baseline

Measure: Rhythm and Rate control

Time: 24 hours

Other Outcomes

Description: hypotension during hospitalisation, bradycardia, chest pain, allergic reaction

Measure: Arterial hypotension Bradycardia (HR <45 bpm) Other (chest pain, allergic reaction……)

Time: 24 hours

11 A Phase II Trial of Induction Chemotherapy With ND-420, Cisplatin and Fluorouracil Followed by Surgery in the Treatment of Patients With Localized Squamous Cell Carcinoma of the Esophagus

Investigator will assign 53 patients who had been histologically proven localized squamous cell carcinoma of esophagus to receive the induction chemotherapy regimen of ND-420 50 mg/m2 on day 1, cisplatin 70 mg/m2 on day1, plus fluorouracil 700 mg/m2 daily, day1 to day4, every 3 weeks for 2 cycles and then followed by surgical resection. The successful rate of complete treatment per protocol and complete resection will be the primary variant to evaluate in our study.

NCT02017600
Conditions
  1. Localized Squamous Cell Carcinoma of the Esophagus
Interventions
  1. Drug: ND-420
  2. Procedure: Surgery
  3. Drug: Cisplatin
  4. Drug: fluorouracil
MeSH:Carcinoma Carcinoma, Squamous Cell Esophageal Neoplasms Esophageal Squamous Cell Carcinoma
HPO:Carcinoma Esophageal neoplasm Squamous cell carcinoma

the correlation between clinical outcomes and the potential predictive genomic biomarkers(B-tubulin mutation, p53-Arg 72Pro, Bcl2-C938A, MDR1-C3435T polymorphism, TNFRSF1B-1466, GSTP1-l105V, CYP1B1, TS-5'UTR) for tumor response. --- C938A --- --- C3435T ---

Primary Outcomes

Measure: the R0 resection rate of participants

Time: up to three months

Secondary Outcomes

Measure: the response rate (RECIST) of participants

Time: up to three months

Measure: Number of participants with adverse events as a measure of safety and tolerability

Time: up to one year

Measure: the population pharmacokinetic parameters (Cmax, AUC... )of ND-420 in the participants

Time: 0, 30min, 1hr of ND-420 infusion. selected randomly form one of 3hr, 7hr, 11hr and 23hr after the end of ND-420 infusion.

Measure: the correlation between clinical outcomes and the potential predictive genomic biomarkers(B-tubulin mutation, p53-Arg 72Pro, Bcl2-C938A, MDR1-C3435T polymorphism, TNFRSF1B-1466, GSTP1-l105V, CYP1B1, TS-5'UTR) for tumor response

Time: up to one year

Measure: 1-year survival rate of participants

Time: up to one year

Measure: pathologic complete response rate of participants

Time: up to one year

Measure: 1-year progression free survival rate of participants

Time: up to one year

Measure: 1-year overall survival rate of participants

Time: up to one year

12 CYP2D6 Screening for Adverse Drug Reactions to Codeine in Breast Milk

The purpose of this study is to determine if non-invasive salivary genetic screening of breastfeeding mothers taking codeine will allow for the successful identification of mother-infant pairs susceptible to adverse events and to prevent these adverse events by personalizing their medication to their genetics.

NCT01050400
Conditions
  1. Cytochrome P450 2D6 Ultra-rapid Metabolism
Interventions
  1. Genetic: Cytochrome P450 2D6 (CYP2D6) genetic screening.
MeSH:Drug-Related Side Effects and Adverse Reactions

Incidence of the C3435T polymorphism in the multi-drug resistance gene (MDR1) which has been associated with significantly greater pain relief from morphine treatment.. null. --- C3435T ---

Primary Outcomes

Measure: Incidence of maternal and neonatal CNS depression in the prospective pharmacogenetic screening group to that of a retrospectively screened population

Time: 5-8 days post c-section surgery

Secondary Outcomes

Measure: Incidence of the phase II uridine diphosphate glucuronyltransferase 2B7 (UGT2B7)*2/*2 variant which has been associated with higher morphine 6-glucuronide to morphine ratios.

Time: Minimum 1 week prior to c-section

Measure: Incidence of the C3435T polymorphism in the multi-drug resistance gene (MDR1) which has been associated with significantly greater pain relief from morphine treatment.

Time: Minimum 1 week prior to c-section

Measure: Incidence of the A118G polymorphism in the opioid receptor 1 (OPRM1) which has been associated with reduced response to morphine treatment.

Time: Minimum 1 week prior to c-section

13 Investigation Drug-drug Interaction Between Dabigatran and Clarithromycin

Dabigatran (Pradaxa ®) is a new oral anticoagulant. It is used to prevent venous thromboembolism in orthopedic surgery and has recently demonstrated efficacy and safety at least as good as anticoagulants in the prevention of thromboembolism in atrial fibrillation and the treatment of venous thromboembolism. It is administered with fixed dose and does not require laboratory monitoring because of the low inter and intra individual pharmacokinetic (PK) and pharmacodynamics (PD) of dabigatran. However, the bioavailability of dabigatran is very low (6.5%) and is controlled by an efflux protein, P-GP. This molecule has a genetic polymorphism. The inhibition of this protein can cause a significant increase in intestinal absorption of dabigatran and expose patients to a risk of bleeding by overdose. Two major drug interactions have been identified : quinidine (cons-indication) and amiodarone (precautions). It is likely that other interactions exist and can be clinically significant in patients not selected such as testing. The development of tools to study the influence of P-GP on the PK and PD of dabigatran is therefore interesting. As the P-GP has a genetic polymorphism, the study of the latter is an important element in the detection of drug interactions. In this sense, clarithromycin, a potent inhibitor of P-GP is a good model to evaluate the primary mechanism of drug interaction of dabigatran and optimize the experimental design of studies to be conducted.

NCT01385683
Conditions
  1. Healthy
Interventions
  1. Drug: Dabigatran then dabigatran and clarithromycin
  2. Drug: Clarithromycin and dabigatran then dabigatran

Genotyping of MDR-1 (gene for P-GP): C3435T SNP of exon 26, SNP G2677T / A of exon 21 and C1236T SNP of exon 12. Inclusion Criteria: - affiliated or beneficiary of a social security category - having signed the inform consent form - having signed the genetic consent form - weight between 60 and 85 kg - normal clinical exam - normal biological exam Exclusion Criteria: - contra-indication to dabigatran - contra-indication to clarithromycin - previous history of psychiatric disease, or antidepressant treatment, or convulsion, or hemorrhagic disease - smoker - peptic ulcer - severe liver disease - severe kidney failure - previous surgery within one month Inclusion Criteria: - affiliated or beneficiary of a social security category - having signed the inform consent form - having signed the genetic consent form - weight between 60 and 85 kg - normal clinical exam - normal biological exam Exclusion Criteria: - contra-indication to dabigatran - contra-indication to clarithromycin - previous history of psychiatric disease, or antidepressant treatment, or convulsion, or hemorrhagic disease - smoker - peptic ulcer - severe liver disease - severe kidney failure - previous surgery within one month Healthy null --- C3435T ---

Primary Outcomes

Description: Calculating the area under the curve (AUC) from plasma concentrations of dabigatran versus time by the trapezoidal method. Determination of maximum concentration (Cmax)

Measure: Determination of dabigatran and its metabolites in plasma by LC/MS-MS method

Time: At Day 4 and Day 11

Secondary Outcomes

Description: Measures activated Partial Thromboplastin Time (aPTT)and measures ECarin Time (ECT),

Measure: Pharmacodynamic parameters

Time: At Day 4 and Day 11

Description: Genotyping of MDR-1 (gene for P-GP): C3435T SNP of exon 26, SNP G2677T / A of exon 21 and C1236T SNP of exon 12

Measure: Genotyping

Time: At Day 1

14 An Open Non Randomized Comparative Study Exploring Drug Interaction Between Colchicine and Calcineurin Inhibitors in 2 Groups (Ciclosporin Group and Tacrolimus Group) of Renal Graft Recipients

Ciclosporin inhibits P-glycoprotein should increase colchicine bioavailability whereas tacrolimus should not influence colchicine disposition. This is a prospective, controlled, open labeled study performed in renal graft recipients comparing colchicine single dose (1mg) pharmacokinetics in 14 patients treated with tacrolimus and 14 patients treated with cyclosporin.

NCT01160276
Conditions
  1. Renal Replacement Therapies
Interventions
  1. Drug: cyclosporine+colchicine
  2. Drug: tacrolimus

ABCB1 Haplotypes composed of 3 SNPs: C3435T, G2677T / A and C1236T.. null. --- C3435T ---

Primary Outcomes

Measure: Area under the curve of plasma concentration of colchicine over time 0-∞

Time: 4 weeks

Secondary Outcomes

Measure: Half-life of colchicine (T1/2).

Time: 4 weeks

Measure: AUC0-3h colchicine to focus the analysis on the absorption phase (argument in favor of an interaction-dependent P-gp)

Time: 4 weeks

Measure: Cmax observed colchicine.

Time: 4 weeks

Measure: Residual tacrolimus or cyclosporine concentrations

Time: 4 weeks

Measure: ABCB1 genotype at position 3435 (rs 1045642) or 3435 cc, 3435TT, heterozygotes could not be included in the tacrolimus group.

Time: 4 weeks

Measure: ABCB1 Haplotypes composed of 3 SNPs: C3435T, G2677T / A and C1236T.

Time: 4 weeks

Measure: CYP3A5 Genotype: search for the allele * 1 (rs 776746): 3 possible genotypes CYP3A5 * 3 / * 3 - CYP3A5 * 3 / * 1 - CYP3A5 * 1 / * 1.

Time: 4 weeks

Measure: GFR calculated by MDRD formula.

Time: 4 weeks

Measure: BMI

Time: 4 weeks

Measure: Drug related (azathioprine, mycophenolic acid, diuretics, ACE inhibitors, ARAII)

Time: 4 weeks

15 Use of a Simplified Nomogram and Pharmacogenetics to Individualize Digoxin Dosing in Heart Failure Patients vs. Standard Care

Dosing methods for digoxin, a drug used to treat heart failure, have not been updated in decades despite evidence in recent years suggesting that blood levels of digoxin achieved with traditional dosing practices may increase the risk of adverse events. We developed a simple dosing tool that targets lower blood levels of digoxin that have been associated with improved outcomes compared to higher blood levels. The aim of this study is to determine if this simplified dosing tool is more effective than standard digoxin dosing practices at achieving lower blood levels and also to determine if digoxin dosing may be further optimized by incorporating patients' genetic information believed to influence the drug's properties.

NCT01005602
Conditions
  1. Heart Failure
Interventions
  1. Other: Digoxin Dosing per Nomogram
  2. Drug: Digoxin
MeSH:Heart Failure
HPO:Abnormal left ventricular function Congestive heart failure Right ventricular failure

We compared serum digoxin concentrations by ABCB1 genotype.. Serum Digoxin Concentration by ABCB1 SNP C3435T. --- C3435T ---

Serum digoxin concentration by genotypes for the ABCB1 SNP C3435T. --- C3435T ---

Primary Outcomes

Measure: Percent of Patients Achieving a Desired Steady-state Serum Digoxin Concentration Between 0.5 - 0.9ng/ml

Time: Steady-state (2 - 4 weeks after initiation)

Secondary Outcomes

Measure: Mean Serum Digoxin Concentration

Time: Steady-state (2 - 4 weeks after initiation)

Measure: Serum Digoxin Concentration < 1.0 ng/ml

Time: Steady-state (2 - 4 weeks after initiation)

Description: 55 patients in the Digoxin Dosing per Nomogram group consented to the Pharmacogenetic substudy and provided blood samples to perform pharmacogenetic analyses. We compared serum digoxin concentrations by ABCB1 genotype.

Measure: Serum Digoxin Concentration by ABCB1 Single Nucleotide Polymorphism (SNP) C1236T

Time: Steady-state (2 - 4 weeks after initiation)

Description: Serum digoxin concentration by genotypes for the ABCB1 SNP C3435T

Measure: Serum Digoxin Concentration by ABCB1 SNP C3435T

Time: Steady-state (2 - 4 weeks after initiation)

Description: Serum digoxin concentration by ABCB1 SNP genotypes

Measure: Serum Digoxin Concentration by ABCB1 SNP G2677T/A

Time: Steady-state (2 - 4 weeks after initiation)

16 Utilizing Pharmacogenetics to Predict Drug Interactions in Kidney Transplant Recipients

Solid organ transplant recipients would greatly benefit from pharmacogenetic evaluation since immunosuppressive drug regimens consist of multiple medications with narrow therapeutic ranges and toxic adverse event profiles. Tacrolimus is a potent immunosuppressive agent utilized for rejection prophylaxis. Intensive pharmacokinetic monitoring must be performed following organ transplantation to ensure therapeutic drug concentrations due to its highly variable pharmacokinetics profile and narrow therapeutic index. Tacrolimus is a substrate for CYP450 3A and for the membrane transporter p-glycoprotein (Pgp). Polymorphisms in the gene encoding for CYP3A5 have been extensively studied and have been found to influence the dosing of tacrolimus. The effect of ABCB1 gene polymorphisms (which encodes for Pgp) upon tacrolimus pharmacokinetics has been more difficult to establish. This study will determine if haplotypes derived from three frequent polymorphisms in the ABCB1 gene (C1236T, G2677T, C3435T) can predict the degree of drug interaction between tacrolimus (CYP3A5/Pgp substrate) and ketoconazole (CYP3A5/Pgp inhibitor) in patients who are CYP3A5 nonexpressors. This prospective pharmacokinetic and pharmacogenomic study will enroll 20 stable renal transplant recipients with the CYP3A5 *3/*3 genotype and grouped by ABCB1 haplotype (CGC vs TTT). Pharmacokinetics of tacrolimus will be assessed on 2 occasions with and without ketoconazole coadministration separated by 1 week. The order of study occasions will be randomized in a crossover design. The results of this study may identify a genomic marker for predicting drug-drug interactions. Knowing this information a priori will aid clinicians in modifying drug dosing and alleviate patients of the burden of significant drug toxicities.

NCT01288521
Conditions
  1. Kidney Transplantation
Interventions
  1. Drug: Tacrolimus + Ketoconazole, Then Tacrolimus alone
  2. Drug: Tacrolimus alone, Then Tacrolimus + Ketoconazole

This study will determine if haplotypes derived from three frequent polymorphisms in the ABCB1 gene (C1236T, G2677T, C3435T) can predict the degree of drug interaction between tacrolimus (CYP3A5/Pgp substrate) and ketoconazole (CYP3A5/Pgp inhibitor) in patients who are CYP3A5 nonexpressors. --- C1236T --- --- G2677T --- --- C3435T ---

Primary Outcomes

Description: Tac bioavailability alone vs. Tac bioavailability with Keto. To determine F we took the ratio of area under the curve of the oral dose divided by the area under the curve of the IV dose. F was determined by fitting a model that considered the plasma concentration of tac with IV vs. oral dosing.

Measure: Tacrolimus Bioavailability (F)

Time: baseline and 2 weeks


HPO Nodes


HP:0001635: Congestive heart failure
Genes 264
TLL1 DSP PLN SLC25A26 BSCL2 DSP NDUFB11 ACTC1 RET TRNL1 JUP CAV1 TRNK SGCD ACTC1 KCNJ5 GTF2IRD1 TRNC FXN WRN HBA2 TTN CAVIN1 VHL ATP6V1A PPA2 FGFR3 MYH7 TRNS2 EYA4 PLOD1 LMNA BMP2 KIF1B SLC2A10 NDUFB8 GNA11 CACNA1S ND1 HADHA TCF4 GAA TRNK VCL GATA6 TBL2 MYL3 PLOD1 ABCC6 GNPTAB SDHD STRADA PNPLA2 ENG LMNA CLIP2 RFC2 TAZ TPI1 COL1A2 BAG3 LIMK1 DSP GTPBP3 DES IRF5 NDUFAF1 ELN SELENON PSMB8 HJV MYD88 MYH6 AGGF1 EYA4 ATP5F1A TET2 ND6 HFE DMD MST1 MAPRE2 DLST DNMT3A TNNI3K TUBB TNNT2 EFEMP2 TRIP4 DNAJC19 XYLT1 TRNQ SDHB GDNF ADCY5 EPAS1 GDF2 PRKAG2 PSEN2 CCR6 AFF4 COL1A1 CDH23 CITED2 ENPP1 RAB3GAP2 BCHE FLNC GLA SF3B1 TRNW HADHA DES IFIH1 MECP2 TMEM70 GATAD1 ACAD9 HBB ACVRL1 HADHB MTTP RASA1 TMEM127 FGF23 NF1 PRDM16 SDHAF2 PRKAR1A FGD1 LMNA NDUFAF3 TNNI3 RBM20 VHL IKBKG VPS33A XYLT2 MYH6 SDHD TRPM4 GLB1 ALMS1 SDHD COX1 TPM1 AGPAT2 SCN5A CLIC2 SCO2 LMNA CAV1 SDHA LMNA HAMP RYR1 CASR MYH7 TRIM37 KIF1B LMNA PTEN SURF1 ACTN2 MYH7 RET LMNA ATXN7 LMNA SLC19A2 GTF2I RPS19 MYH7 TRNF STAT1 GTPBP3 PPARG TRNV TMEM127 LDB3 MAX TBX20 TRNS1 COX2 MDH2 SCO1 MYLK2 GJA1 HFE NDUFS2 GK TTN ELAC2 HNRNPA2B1 IDS TBX20 TRNE MAX NSMCE2 ACAD9 TRNK CYTB GATA4 ND5 GLA ADCY5 HBA1 HADHB SNAP29 MYH7 NKX2-5 SLC22A5 SDHC HBB CITED2 HLA-DRB1 HNRNPA1 ABCC6 SDHB SLC25A3 ALMS1 CP VCP SCN4A HBB FH FBN1 DTNA FOS PRKAR1A TF SDHB COG7 VHL TLL1 PPARG FLNA ENG PSEN1 CCN2 MYPN GPR35 BAZ1B JUP EPG5 SLC25A11 RET CLIC2 COX3 FBLN5 SLC17A5 CAV3 NKX2-5 CEP19 TMEM43 PEX7 SMAD4 PHYH CYTB SCN1B MYSM1 ADAMTSL2 PRKAR1A TRNL1