Lerman C, Caporaso N E, Bush A, Zheng Y L, Audrain J, Main D, Shields P G
Psychiatry Department, University of Pennsylvania Health Sciences, Philadelphia, PA, USA.
Am J Med Genet. 2001 Aug 8;105(6):518-20. doi: 10.1002/ajmg.1476.
Approximately 50% of the variance in smoking behavior is attributable to genetic factors. Genes in the serotonin system are plausible candidates because of serotonin's role in mood regulation. The present study examined the association of smoking behavior with a polymorphism in the TPH gene, which codes for a rate limiting enzyme in the biosynthesis of serotonin. A polymorphism in intron 7 has been linked with a variety of traits involving poor impulse control. Participants in this study were 249 Caucasian smokers and 202 nonsmokers recruited through newspaper advertisements. Smokers completed smoking history and nicotine dependence assessments. The overall frequencies of the A- and C-allele were 42% and 58%, respectively. There was no association of TPH alleles with smoking status. However, case series analysis indicated that individuals with the A/A genotype started smoking at age 15.6 years, compared with 17.3 years among smokers with other genotypes. This association was significant in a multivariate regression model controlling for age, education, body mass index (BMI), alcohol use, and medication use. This finding is consistent with previous studies relating the A-allele to impulsive behavior and suggests that it may predispose to early smoking initiation. Future family-based studies are needed to confirm this finding. Published 2001 Wiley-Liss, Inc.
吸烟行为中约50%的差异可归因于遗传因素。血清素系统中的基因是合理的候选基因，因为血清素在情绪调节中起作用。本研究调查了吸烟行为与TPH基因多态性的关联，该基因编码血清素生物合成中的一种限速酶。内含子7中的一种多态性与多种涉及冲动控制不良的性状有关。本研究的参与者是通过报纸广告招募的249名白人吸烟者和202名非吸烟者。吸烟者完成了吸烟史和尼古丁依赖评估。A等位基因和C等位基因的总体频率分别为42%和58%。TPH等位基因与吸烟状态没有关联。然而，病例系列分析表明，A/A基因型的个体在15.6岁开始吸烟，而其他基因型的吸烟者为17.3岁。在控制年龄、教育程度、体重指数（BMI）、饮酒和药物使用的多变量回归模型中，这种关联具有显著性。这一发现与先前将A等位基因与冲动行为相关的研究一致，并表明它可能易导致早期开始吸烟。未来需要基于家庭的研究来证实这一发现。2001年由Wiley-Liss公司出版。
