Division of Clinical Epidemiology & Aging Research, German Cancer Research Center, Bergheimer Str 20, D-69115 Heidelberg, Germany.
Pharmacogenomics. 2010 Apr;11(4):527-36. doi: 10.2217/pgs.10.1.
Genetic contributions to nicotine dependence have been demonstrated repeatedly, but the relevance of individual polymorphisms for smoking cessation remains controversial.
MATERIALS & METHODS: We examined genotypes at two dopamine-related loci, DRD2/ANKK1 (rs1800497) and DBH (rs77905), in 577 heavy smokers participating in a prospective study of smoking cessation in general care in Germany.
Smoking status after 1 year was significantly associated with DRD2/ANKK1, odds of abstinence being 4.4-fold (95% CI: 1.5-12.9) increased in TT- versus CC-homozygous subjects (p = 0.008). No effect was observed for the DBH genotype. The smoking cessation drug bupropion appeared to be particularly effective in CC-homozygotes (among CC subjects there was a 28% higher cessation probability among those taking buproprion; among T carrier subjects there was an increase only by 12%).
The large effects observed for DRD2/ANKK1 might be related to our study design, in which individual therapy was decided by the physician. Further studies are needed to clarify the genetic effects of DRD2/ANKK1 especially in 'real-life' settings outside clinical trials.
遗传因素对尼古丁依赖的影响已得到反复证实，但个体多态性对戒烟的相关性仍存在争议。
我们在德国普通医疗环境下的一项前瞻性戒烟研究中，检测了 577 名重度吸烟者中两个与多巴胺相关的基因座 DRD2/ANKK1（rs1800497）和 DBH（rs77905）的基因型。
1 年后的吸烟状况与 DRD2/ANKK1 显著相关，与 CC 纯合子相比，TT 纯合子的戒烟几率增加了 4.4 倍（95%CI：1.5-12.9）（p=0.008）。DBH 基因型无影响。戒烟药物安非他酮似乎对 CC 纯合子特别有效（在 CC 受试者中，服用安非他酮的戒烟概率增加 28%；而在 T 携带者中，仅增加 12%）。
DRD2/ANKK1 观察到的较大影响可能与我们的研究设计有关，在该设计中，个体治疗由医生决定。需要进一步的研究来阐明 DRD2/ANKK1 的遗传效应，特别是在临床试验以外的“现实生活”环境中。
