The role of CYP2A6 in the emergence of nicotine dependence in adolescents
The role of CYP2A6 in the emergence of nicotine dependence in adolescents
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DOI：
10.1542/peds.2006-1583
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发表时间：
2007-01-01
期刊：
影响因子：
8
通讯作者：
Tyndale, Rachel F.
中科院分区：
文献类型：
--
作者：
Audrain-McGovern, Janet;Al Koudsi, Nael;Tyndale, Rachel F.
目标。本研究的目的是评估尼古丁代谢失活的遗传变异是否与青春期中后期尼古丁依赖的出现有关，以及最初的吸烟经历是否介导了这种影响。参与者是222名欧洲血统的青少年，他们参加了一项关于青少年吸烟的生物行为决定因素的纵向队列研究。调查数据每年收集一次，从9年级到12年级结束。自我报告测量包括尼古丁依赖、吸烟、首次吸烟年龄、首次吸烟经历、同伴和家庭成员吸烟、酒精和大麻使用情况。通过口腔拭子收集DNA，评估在白人中常见的CYP2A6等位基因，并证明其降低酶功能（CYP2A6*2, *4, *9, *12）。潜在生长曲线模型表明，正常代谢者（没有检测到CYP2A6变异的个体）以更快的速度发展尼古丁依赖，与代谢较慢的个体（CYP2A6变异的个体）相比，尼古丁依赖的增加更慢。最初的吸烟经历并不能解释CYP2A6基因变异如何影响尼古丁依赖。这些发现可能有助于更好地了解吸烟行为的生物学和青少年尼古丁依赖的出现，并为未来旨在了解青少年吸烟行为中遗传、社会和心理因素之间复杂相互作用的工作提供信息。
OBJECTIVES. The objectives of our study were to evaluate whether genetic variation in nicotine metabolic inactivation accounted for the emergence of nicotine dependence from mid- to late adolescence and whether initial smoking experiences mediated this effect.METHODS. Participants were 222 adolescents of European ancestry who participated in a longitudinal cohort study of the biobehavioral determinants of adolescent smoking. Survey data were collected annually from grade 9 to the end of grade 12. Self-report measures included nicotine dependence, smoking, age first smoked, initial smoking experiences, peer and household member smoking, and alcohol and marijuana use. DNA collected via buccal swabs was assessed for CYP2A6 alleles that are common in white people and are demonstrated to decrease enzymatic function (CYP2A6*2, *4, *9, *12).RESULTS. Latent growth-curve modeling indicated that normal metabolizers (individuals with no detected CYP2A6 variants) progressed in nicotine dependence at a faster rate and that these increases in nicotine dependence leveled off more slowly compared with slower metabolizers (individuals with CYP2A6 variants). Initial smoking experiences did not account for how CYP2A6 genetic variation impacts nicotine dependence.CONCLUSIONS. These findings may help to promote a better understanding of the biology of smoking behavior and the emergence of nicotine dependence in adolescents and inform future work aimed at understanding the complex interplay between genetic, social, and psychological factors in adolescent smoking behavior.