Psychobiological /Genetic Determinants-Smoking Cessation

心理生物学/遗传决定因素——戒烟

• 批准号: 7106368
• 负责人: SEAN P. DAVID
• 金额: $ 16.11万
• 依托单位: MEMORIAL HOSPITAL OF RHODE ISLAND
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-09-27 至 2008-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7106368
• 关键词: amine oxidase (flavin); bupropion; catechol methyltransferase; clinical research; clinical trials; craving; cues; dopamine beta monooxygenase; dopamine receptor; dopamine transporter; drug abuse chemotherapy; gene environment interaction; genetic markers; genetic polymorphism; genotype; human subject; human therapy evaluation; patient oriented research; pharmacogenetics; placebos; psychopharmacology; smoking; smoking cessation; tobacco abuse; tyrosine 3 monooxygenase

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.

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，以成为戒烟研究的独立研究者，重点是分子遗传学。这项K08指导的临床科学家奖提案概述了一项全面的五年监督研究计划，该计划在药物遗传戒烟临床试验中与赞助商Raymond Niaura博士进行了临床试验。在布朗大学和乔治敦大学医学博士的共同提案者彼得·希尔兹（Peter Shields），与布朗大学的跨学科烟草使用研究中心相结合的结构化教学研讨会系列，结合了乔治敦大学的基因分型技术培训，并在布朗大学建立了一所独立实验室。这项工作将由跨学科导师的杰出网络和牛津大学共同提案者的杰出网络告知。拟议的研究的重点是评估多巴胺转运蛋白转运蛋白SLC6A3多态性以及其他多巴胺能候选基因多态性在吸烟者对盐酸盐盐酸化剂中的治疗反应中的作用。拟议的研究将是探讨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的研究，以降低吸烟的增强特性并影响吸烟结果。 具体目的是： （1）评估多巴胺转运蛋白SLC6A3多态性在对安非他酮的治疗反应中的作用， （2）测试假说，即安非他振降低吸烟的增强特性，以及携带DRD2-TAQ1 A2/A2基因型的吸烟者在吸烟的吸烟者中的降低对吸烟的增强特性的影响要比吸烟中的吸烟者要大得多。 （3）研究吸烟者与DRD2-TAQ1 A2/A2和DRD2-TAQ1 A1/A1/A1或A1/A2基因型的相互作用和提示反应性之间的相互作用 （4）评估额外多巴胺能候选基因多态性对对安非他酮的治疗反应的影响，以戒烟和多种内表型。

项目成果

Successful Latino community partnership program for smoking cessation.

成功的拉丁裔社区戒烟合作计划。

• DOI: 10.2105/ajph.2007.111237
• 发表时间: 2007
• 期刊: American journal of public health
• 影响因子: 12.7
• 作者: David,SeanP;Smith,Marcia;Lee,ChristinaS;Sullivan,Garrett
• 通讯作者: Sullivan,Garrett

Relationship between amounts of daily cigarette consumption and abdominal obesity moderated by CYP2A6 genotypes in Chinese male current smokers.

• DOI: 10.1007/s12160-011-9318-5
• 发表时间: 2012-04
• 期刊: Annals of behavioral medicine : a publication of the Society of Behavioral Medicine
• 作者: Liu T;David SP;Tyndale RF;Wang H;Yu XQ;Chen W;Zhou Q;Chen WQ
• 通讯作者: Chen WQ

Associations of CYP2A6 genotype with smoking behaviors in southern China.

• DOI: 10.1111/j.1360-0443.2010.03353.x
• 发表时间: 2011-05
• 期刊: Addiction (Abingdon, England)
• 作者: Liu T;David SP;Tyndale RF;Wang H;Zhou Q;Ding P;He YH;Yu XQ;Chen W;Crump C;Wen XZ;Chen WQ
• 通讯作者: Chen WQ

A cost-effectiveness analysis of genetic testing of the DRD2 Taq1A polymorphism to aid treatment choice for smoking cessation.

DRD2 Taq1A 多态性基因检测的成本效益分析，以帮助选择戒烟治疗。

• DOI: 10.1080/14622200701767761
• 发表时间: 2008
• 期刊: Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco
• 作者: Welton,NickyJ;Johnstone,ElaineC;David,SeanP;Munafò,MarcusR
• 通讯作者: Munafò,MarcusR

Building a successful research enterprise in family medicine: the Brown experience.

建立成功的家庭医学研究企业：布朗经验。

• 发表时间: 2006
• 期刊: Medicine and health, Rhode Island
• 作者: David,SeanP;Eaton,CharlesB;Culpepper,Larry;Goldman,RobertaE;Lavallee,LauraK;Simmons,EmmaM
• 通讯作者: Simmons,EmmaM