Breitling Lutz Philipp, Dahmen Norbert, Mittelstrass Kirstin, Illig Thomas, Rujescu Dan, Raum Elke, Winterer Georg, Brenner Hermann
Division of Clinical Epidemiology and Aging Research, German Cancer Research Center, Heidelberg, Germany.
Biol Psychiatry. 2009 Apr 15;65(8):691-5. doi: 10.1016/j.biopsych.2008.10.004. Epub 2008 Nov 8.
Evidence has recently accumulated that single nucleotide polymorphisms in the genetic region encoding the nicotinic acetylcholine receptor subunits alpha-5, alpha-3, and beta-4 are associated with smoking and nicotine dependence. We aimed to determine whether these genetic variations are also predictive of smoking cessation.
Lifetime history of smoking was assessed by questionnaire at enrolment into a large epidemiological study of the German elderly population (ESTHER study). Cox proportional hazards modeling was applied in a retrospective cohort approach to determine the associations of individual polymorphisms and haplotypes with smoking cessation probability in 1446 subjects who reported regularly smoking more than 20 cigarettes at some point in their lives.
Given the genotype distributions and number of cessation events observed, the power to detect associations ranged from 54% to 97% for hazard ratios of 1.2 to 1.4 in case of the variant with strongest prior evidence (alpha = .05). Nonetheless, neither individual polymorphisms nor inferred multilocus haplotypes were significantly associated with smoking cessation.
Although the robust association of the nicotinic acetylcholine receptor subunit genes investigated with smoking-related phenotypes is an apparent success story of genetic epidemiology, the respective variations seem to exert no relevant influence on smoking cessation probability in heavy smokers in the general population.
最近有证据表明，编码烟碱型乙酰胆碱受体α-5、α-3和β-4亚基的基因区域中的单核苷酸多态性与吸烟和尼古丁依赖有关。我们旨在确定这些基因变异是否也能预测戒烟情况。
在一项针对德国老年人群的大型流行病学研究（ESTHER研究）入组时，通过问卷调查评估吸烟的终生史。采用Cox比例风险模型，以回顾性队列研究方法，在1446名报告在其生命中的某个时刻经常每天吸烟超过20支的受试者中，确定个体多态性和单倍型与戒烟概率的关联。
鉴于观察到的基因型分布和戒烟事件数量，对于先前证据最充分的变异（α = 0.05），当风险比为1.2至1.4时，检测关联的效能范围为54%至97%。尽管如此，个体多态性和推断的多位点单倍型均与戒烟无显著关联。
尽管所研究的烟碱型乙酰胆碱受体亚基基因与吸烟相关表型之间的强烈关联是遗传流行病学的一个明显成功案例，但在一般人群的重度吸烟者中，相应变异似乎对戒烟概率没有相关影响。
