Division of Clinical Epidemiology & Aging Research, German Cancer Research Center (DKFZ), TP4/INF581, 69120 Heidelberg, Germany.
Pharmacogenomics. 2011 Aug;12(8):1099-106. doi: 10.2217/pgs.11.74. Epub 2011 Aug 1.
Several studies have provided evidence for associations of polymorphisms located in and near dopamine-related genes and nicotine dependence and other smoking-related phenotypes, including pharmacogenetic interactions.
The purpose of the present work was to examine the association of SNPs in the DOPA decarboxylase (DDC), dopamine receptor D2 (DRD2) and dopamine transporter (SLC6A3) genes with smoking cessation in a large retrospective study featuring approximately 900 cessation events.
MATERIALS & METHODS: Data originated from the enrollment questionnaire of the epidemiological ESTHER study of community-dwelling adults aged 50-74 years, conducted in the German state of Saarland between July 2000 and December 2002. Restricting the analyses to subjects who reported to have regularly smoked > 20 cigarettes per day at some point in their life, we used survival analysis methods to model the time from initiation of regular smoking to cessation (defined as quitting with abstinence lasting until enrollment) and its relation with eight polymorphisms in the aforementioned genes (five in DDC, two in DRD2 and one in SLC6A3) in 1446 participants.
Neither individual variants nor DDC haplotypes were associated with the probability of overcoming nicotine dependence in this cohort.
The repeated suggestion of associations between the variants examined and nicotine dependence in previous reports seems to contrast the negative results in the present study. This would appear consistent with the hypothesis that the establishment of regular heavy smoking might abolish associations between genetic determinants of nicotine dependence and nicotine dependence-related phenotypes, in particular the probability of successful smoking cessation.
多项研究提供了位于多巴胺相关基因及其附近的多态性与尼古丁依赖和其他与吸烟相关表型（包括遗传药理学相互作用）之间关联的证据。
本研究旨在通过一项包含大约 900 个戒烟事件的大型回顾性研究，检查多巴脱羧酶（DDC）、多巴胺受体 D2（DRD2）和多巴胺转运蛋白（SLC6A3）基因中的 SNP 与戒烟的关联。
数据来源于在德国萨尔州于 2000 年 7 月至 2002 年 12 月进行的 50-74 岁社区居住成年人的流行病学 ESTHER 研究的入组问卷。将分析限制在报告一生中曾定期吸食>20 支香烟的受试者中，我们使用生存分析方法来模拟从开始定期吸烟到戒烟的时间（定义为戒烟后直至入组前持续禁欲）及其与上述基因中的 8 个多态性（DDC 中的 5 个、DRD2 中的 2 个和 SLC6A3 中的 1 个）在 1446 名参与者中的关系。
在该队列中，个体变体或 DDC 单倍型均与克服尼古丁依赖的概率无关。
以前的报告中反复提出所检查的变体与尼古丁依赖之间存在关联，而本研究的阴性结果似乎与之形成对比。这似乎与以下假设一致，即建立定期大量吸烟可能会消除尼古丁依赖遗传决定因素与尼古丁依赖相关表型（特别是成功戒烟的可能性）之间的关联。
