Kubota T, Nakajima-Taniguchi C, Fukuda T, Funamoto M, Maeda M, Tange E, Ueki R, Kawashima K, Hara H, Fujio Y, Azuma J
Department of Clinical Evaluation of Medicines and Therapeutics, Graduate School of Pharmaceutical Sciences, Osaka University, Yamadaoka, Suita City, Japan.
Pharmacogenomics J. 2006 Mar-Apr;6(2):115-9. doi: 10.1038/sj.tpj.6500348.
CYP2A6 is the main enzyme that catalyzes nicotine into cotinine. Interindividual differences in nicotine metabolism result at least partially from polymorphic variation of CYP2A6 gene. In this study, we evaluated the influence of CYP2A6 polymorphisms on clinical phenotypes of smoking, such as smoking habit and withdrawal symptoms. Japanese smokers (n = 107) were genotyped for CYP2A6*1, *4 and 9. Consistent with the previous reports, CYP2A6 genotypes have a tendency to correlate with the number of cigarettes per day and with daily intake of nicotine. Interestingly, CYP2A6 high-activity group (CYP2A61/*1, *1/*9, *1/*4, *9/9) smoked the first cigarette of the day earlier than low-activity group (CYP2A64/*9, *4/*4), indicating more remarkable nicotine dependence. Furthermore, nicotine withdrawal symptoms were more serious in smoking cessation in CYP2A6 high-activity group. Collectively, CYP2A6 genotypes are related with nicotine dependence, influencing smoking habits and withdrawal symptoms in quitting smoking. It is proposed that individualized smoking cessation program could be designed based on CYP2A6 genotypes.
细胞色素P450 2A6（CYP2A6）是催化尼古丁转化为可替宁的主要酶。尼古丁代谢的个体差异至少部分源于CYP2A6基因的多态性变异。在本研究中，我们评估了CYP2A6基因多态性对吸烟临床表型的影响，如吸烟习惯和戒断症状。对107名日本吸烟者进行了CYP2A6 *1、4和9基因分型。与先前的报道一致，CYP2A6基因型倾向于与每日吸烟量和尼古丁日摄入量相关。有趣的是，CYP2A6高活性组（CYP2A6 *1/*1、*1/*9、*1/*4、*9/*9）比低活性组（CYP2A6 *4/*9、*4/*4）更早吸食当天的第一支烟，表明尼古丁依赖性更强。此外，CYP2A6高活性组戒烟时的尼古丁戒断症状更严重。总体而言，CYP2A6基因型与尼古丁依赖性相关，影响吸烟习惯和戒烟时的戒断症状。建议根据CYP2A6基因型设计个性化的戒烟方案。
