Pharmacogenetics Core

该药物开发单位中心(MDU)的药物遗传学核心的目标是 将分子遗传学融入可卡因药物治疗临床试验的设计和实施 依赖。我们将采用前瞻性基因分型方法，根据胸径基因座上的基因对参与者进行分层。 在项目1中和在项目2中的5-羟色胺转运体位置。这个核心有五个特定的目标。(1)在 项目1WE将根据功能启动子多态调控的基因对预期受试者进行分层 然后将其输入安慰剂对照随机分组 双硫仑治疗可卡因依赖的临床试验。(2)在项目2中，我们将对未来的研究对象进行分层 调节5-HTTPLR的功能启动子多态的基因型，然后将它们输入安慰剂 舍曲林治疗可卡因依赖的随机对照临床试验。(3)就项目1和项目2而言，我们 将在GAT-1基因(SLC6A12)中发现新的单核苷酸多态(SNPs)，它编码 GABA转运蛋白，GAT-1。GAT-1为替加宾的治疗靶点，进行了比较 在这两个项目中都是安慰剂。我们将测试GAT-1单倍型与对 替加宾。(4)我们将在GAD-65建立已知非同义SNPs的基因分型基础设施 和GAD-67，以及5-HTTPLR。(5)我们将为基因分型提供技术咨询和支持- 基于当前MDU和NIDA赞助的其他物质使用治疗试验的分析，请访问 耶鲁大学。 该核心支持的设施将就遗传方法(包括统计方法)进行咨询 遗传学)由物质滥用部门的所有教员进行临床试验。分子的整合 遗传学和临床药理学承诺通过以下方式推进药物滥用治疗领域 产生创新的假说并引入新的遗传和神经蛋白质组方法，如 除了物质滥用外，它们还会进化为其他类型的医学障碍。

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.