药物遗传学核心-猫眼课题宝

药物遗传学核心

批准号：

7648024

负责人：

Joseph F. Cubells

金额：

$42.42万

依托单位：

BAYLOR COLLEGE OF MEDICINE

依托单位国家：

美国

项目类别：

财政年份：

2008

资助国家：

美国

项目状态：

已结题

起止时间：

2008-07-01 至 2009-06-30

来源：

https://reporter.nih.gov/project-details/7648024

关键词：

Accounting Alcohol or Other Drugs use American Amino Acid Sequence Antidepressive Agents Bioinformatics Biological Assay Butyric Acid Butyric Acids Candidate Disease Gene Carrier Proteins Clinical Pharmacology Clinical Trials Cocaine Cocaine Dependence Cocaine Users Computer Simulation Consult Consultations Data Depressed mood Development Disease Disulfiram Dopamine Dopamine-beta-monooxygenase Education European Exons Facility Construction Funding Category Faculty GABA transporter Genes Genetic Genetic Databases Genetic Polymorphism Genetic Variation Genotype Goals Grant Haplotypes High Pressure Liquid Chromatography Knowledge Mediating Medical Methadone Methodology Methods Mixed Function Oxygenases Molecular Genetics Nomenclature Outcome Measure Paranoia Participant Patients Pharmaceutical Preparations Pharmacogenetics Pharmacotherapy Pilot Projects Placebo Control Placebos Plasma Polymerase Chain Reaction Population Promoter Regions Proteins Purpose Randomized Randomized Clinical Trials Research Research Infrastructure Research Personnel Restriction Fragment Length Polymorphism Analysis Sampling Scanning Selective Serotonin Reuptake Inhibitor Series Sertraline Single Nucleotide Polymorphism Standards of Weights and Measures Statistical Methods Substance abuse problem Tandem Repeat Sequences Testing Text Therapeutic Time Upper arm Work base design dopamine transporter double-blind placebo controlled trial expectation gabapentin gamma-Aminobutyric Acid genetic variant inhibitor/antagonist innovation neurotransmission novel programs promoter prospective response reuptake serotonin transporter size therapeutic target tiagabine transmission process uptake

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英文摘要

The goal of the Pharmacogenetics CORE of this Medications Development Unit Center (MDU) is to integrate molecular genetics into the design and execution of clinical trials of pharmacotherapies for cocaine dependence. We will employ prospective genotyping to stratify participants by genotype at the DBH locus in Project 1 and at the serotonin transporter locus in Project 2. This CORE has five Specific Aims. (1) In Project 1we will stratify prospective subjects bygenotype at a functional promoter polymorphism regulating levels of dopamine beta hydroxylase (DBH) and then enter them into a placebo controlled randomized clinical trial of disulfiram for cocaine dependence. (2) In Project 2 we will stratify prospective subjects by genotype at a functional promoter polymorphism regulating 5-HTTPLR and then enter them into a placebo controlled randomized clinical trial of sertraline for cocaine dependence. (3) For both Projects 1 and 2 we will identify novel single nucleotide polymorphisms (SNPs) in the GAT-1 gene (SLC6A12), which encodes the GABA transporter protein, GAT-1. The GAT-1 is the therapeutic target of tiagabine, which is compared to placebo in both Projects. We will test for an association between GAT-1 haplotypes and response to tiagabine. (4) We will establish an infrastructure for genotyping known non-synonymous SNPs at GAD-65 and GAD-67, and at the 5-HTTPLR. (5) We will provide technical consultation and support for genotype- based analyses in the current MDUand for other NIDA-sponsored trials for substance-use treatments at Yale. The facilities supported by this CORE will consult on genetic approaches (including statistical genetics) to clinical trials by all the faculty in the Division of SubstanceAbuse. The integration of molecular genetics and clinical pharmacology promises to advance the field of substance abuse treatment by generating innovative hypotheses and introducing new genetic and neuro-proteinomic methodologies as they evolve for other types of medical disorders besides substanceabuse.

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