背景:主要的尼古丁代谢酶CYP2A6的遗传变异,与尼古丁依赖和戒烟有关。尼古丁依赖的严重程度也可以预测戒烟。我们的目标是确定CYP2A6变异和尼古丁依赖如何改变戒烟,以及依赖是否可以完善基于CYP2A6的治疗建议。
方法:成年吸烟者接受安慰剂治疗12周,尼古丁贴片,根据CYP2A6加权遗传风险评分,或伐尼克兰(NCT01314001)被分组为CYP2A6正常(n=567)或慢(n=432)尼古丁代谢者.在基线测量FTND评分,并在治疗结束时评估生化验证的戒烟。
结果:依赖性既不介导也不缓和CYP2A6变异与戒烟之间的关联,在任何治疗臂内,或按血统分层后(n=591欧洲人,n=408非洲血统)或性别(n=444女性,n=555人)。在治疗内分析中,中介效应比值比(OR)为0.95~1.00,偏倚校正后的95%置信区间为1.适度(即,相互作用)效应ORs范围为0.88-1.61(P=0.397-0.828)。对于CYP2A6正常代谢者,高(41.1%)和低(43.4%)依赖者的伐尼克兰戒烟率相似,而那些高与高的人的戒烟率较低对这两个补丁的依赖性低(16.5与29.7%)和安慰剂(8.9vs.18.5%)。CYP2A6代谢慢,高与在所有三个治疗组中,低依赖性具有较低的戒烟率。
结论:虽然尼古丁依赖的严重程度既不介导也不调节CYP2A6与戒烟的关联,纳入有关依赖性的信息可能会优化CYP2A6正常和慢代谢者戒烟治疗辅助的选择。
结论:CYP2A6和尼古丁依赖严重程度的变化会改变戒烟成功率。我们的研究结果表明,虽然尼古丁依赖的严重程度不太可能介导或缓和CYP2A6与戒烟的关联,纳入CYP2A6和尼古丁依赖严重程度的患者信息可能导致戒烟策略的改善.
Genetic variation in Cytochrome P450 2A6 (CYP2A6), the major nicotine metabolizing enzyme, is associated with nicotine dependence and smoking cessation. Nicotine dependence severity also predicts smoking cessation. Our goals were to determine how CYP2A6 variation and nicotine dependence alter smoking cessation, and whether dependence could refine CYP2A6-based treatment recommendations.
Adult smokers treated for 12 weeks with placebo, nicotine patch, or varenicline (NCT01314001) were grouped as CYP2A6 normal (n = 567) or slow (n = 432) nicotine metabolizers based on a CYP2A6 weighted genetic risk score. Fagerström test for nicotine dependence scores were measured at baseline and biochemically verified smoking cessation was assessed at end of treatment.
Dependence neither mediated nor moderated an association between CYP2A6 variation and smoking cessation overall, within any treatment arm, or after stratifying by ancestry (n = 591 European, n = 408 African ancestry) or sex (n = 444 women, n = 555 men). In within-treatment analyses, the mediation effect odds ratio (OR) ranged from 0.95 to 1.00 and the bias-corrected 95% confidence interval contained 1. Moderation (i.e. interaction) effect ORs ranged from 0.88 to 1.61 (p = .397-.828). For CYP2A6 normal metabolizers, quit rates on varenicline were similar for those with high (41.1%) and low (43.4%) dependence, while quit rates were lower for those with high versus low dependence on both patch (16.5 vs. 29.7%) and placebo (8.9 vs. 18.5%). CYP2A6 slow metabolizers with high versus low dependence had lower quit rates in all three treatment arms.
Although nicotine dependence severity neither mediated nor moderated CYP2A6 associations with smoking cessation, incorporating information on dependence may optimize the choice of smoking cessation treatment aid in CYP2A6 normal and slow metabolizers.
Variation in CYP2A6 and nicotine dependence severity alter smoking cessation success. Our findings suggest that while nicotine dependence severity is unlikely to mediate or moderate CYP2A6 associations with cessation, incorporating patient information on both CYP2A6 and nicotine dependence severity may lead to improved smoking cessation strategies.