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 (CYP2A6*1/*1, *1/*9, *1/*4, *9/*9) smoked the first cigarette of the day earlier than low-activity group (CYP2A6*4/*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.
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