Psychobiological /Genetic Determinants-Smoking Cessation

描述（由申请人提供）： 我的职业目标是发展经验，技能和基础设施，成为戒烟研究的独立调查员，重点是分子遗传学。该K 08指导临床科学家奖提案概述了与赞助商Raymond Niaura博士合作的药物遗传学戒烟临床试验监督研究的全面五年计划。和共同赞助人Peter Shields，M.D.在乔治敦大学，一个结构化的教学研讨会系列与跨学科烟草使用研究中心在布朗大学结合实验室培训基因分型技术在乔治敦大学和建立一个独立的实验室在布朗大学。这项工作将由一个杰出的跨学科导师网络和牛津大学共同赞助商的合作研究提供信息。拟议研究的重点是评估多巴胺转运蛋白SLC 6A 3多态性和其他多巴胺能候选基因多态性在吸烟者对盐酸安非他酮戒烟治疗反应中的作用。这项研究将是第一项探索基因型和治疗如何通过多种认知，行为，情感和生理内表型相互作用，以减少吸烟的强化特性并影响吸烟结果的研究。 具体目标是： (1)为了评估多巴胺转运蛋白SLC 6A 3多态性在安非他酮戒烟治疗反应中的作用， (2)为了检验以下假设：安非他酮会减弱吸烟的增强特性，并且安非他酮对吸烟增强特性减弱的影响在携带DRD 2-Taq 1 A2/A2基因型的吸烟者中显著大于携带DRD 2-Taq 1 A1/A1或A1/A2基因型的吸烟者， (3)研究DRD 2-Taq 1 A2/A2和DRD 2-Taq 1 A1/A1或A1/A2基因型吸烟者的基因型和线索反应性之间的相互作用， (4)评价其他多巴胺能候选基因多态性对安非他酮戒烟治疗反应和多种内表型的影响。

DESCRIPTION (provided by applicant): My career goal is to develop the experience, skills, and infrastructure to become an independent investigator in smoking cessation research with a focus on molecular genetics. This K08 Mentored Clinical Scientist Award proposal outlines a comprehensive, five-year program of supervised research in pharmacogenetic smoking cessation clinical trials with Sponsors Raymond Niaura, Ph.D. at Brown University, and Co-Sponsor Peter Shields, M.D. at Georgetown University, a structured didactic seminar series integrated with the Transdisciplinary Tobacco Use Research Center at Brown University combined with laboratory training in genotyping techniques at Georgetown University and establishment of an independent laboratory at Brown University. This work will be informed by an outstanding network of transdisciplinary mentors and collaborative research with Co-Sponsors at the University of Oxford. The focus of the proposed research is an evaluation of the role of the dopamine transporter SLC6A3 polymorphism, and other dopaminergic candidate gene polymorphisms, in treatment response of smokers to bupropion hydrochloride for smoking cessation. The proposed research would be the first study to explore how genotype and treatment interact through multiple cognitive, behavioral, affective, and physiological endophenotypes to reduce the reinforcing properties of smoking and impact smoking outcomes. The specific aims are: (1) To evaluate the role of the dopamine transporter SLC6A3 polymorphism in treatment response to bupropion for smoking cessation, (2) To test the hypotheses that bupropion diminishes the reinforcing properties of smoking and that the effect of bupropion on reduction of the reinforcing properties of smoking will be significantly greater among smokers who carry DRD2-Taq1 A2/A2 genotypes than it is among smokers with DRD2-Taq1 A1/A1 or A1/A2 genotypes, (3) To investigate the interaction between genotype and cue reactivity among smokers with DRD2-Taq1 A2/A2 and DRD2-Taq1 A1/A1 or A1/A2 genotypes, and (4) To evaluate the impact of additional dopaminergic candidate gene polymorphisms on treatment response to bupropion for smoking cessation and multiple endophenotypes.