Johnstone Elaine C, Elliot Katherine M, David Sean P, Murphy Michael F G, Walton Robert T, Munafò Marcus R
Department of Clinical Pharmacology, University of Oxford, Oxford, United Kingdom.
Cancer Epidemiol Biomarkers Prev. 2007 Jun;16(6):1065-9. doi: 10.1158/1055-9965.EPI-06-0936.
We investigated the association of catechol O-methyltransferase (COMT) genotype with abstinence following a smoking cessation attempt among a large cohort of smokers who attempted to quit using either the nicotine transdermal patch or placebo and were followed up over an 8-year period following their initial cessation attempt. In addition, we examined the possible moderating influence of sex on any association. The genotype x treatment interaction effect at 12-week follow-up indicated a greater benefit of active nicotine replacement treatment compared with placebo on likelihood of abstinence in the COMT Met/Met genotype group (33% versus 12%), in comparison to the Met/Val + Val/Val group (22% versus 16%). Our results indicate that COMT genotype may moderate the effect of active transdermal nicotine patch compared with placebo, with reduced relative benefit of nicotine replacement therapy in individuals with Met/Val or Val/Val genotype. Our data follow an emerging pattern of results suggesting that genetic variation in the dopamine pathway may provide a future basis for tailored smoking cessation therapies, but indicate that different genes influencing various components of this pathway may have different effects on response to smoking cessation pharmacotherapy.
我们在一大群尝试戒烟的吸烟者中，研究了儿茶酚-O-甲基转移酶（COMT）基因型与戒烟尝试后戒烟情况之间的关联。这些吸烟者使用尼古丁透皮贴剂或安慰剂尝试戒烟，并在首次戒烟尝试后的8年期间接受随访。此外，我们还研究了性别对这种关联可能产生的调节作用。在12周随访时的基因型x治疗交互效应表明，与安慰剂相比，活性尼古丁替代疗法对COMT Met/Met基因型组的戒烟可能性有更大益处（33%对12%），而Met/Val + Val/Val组为（22%对16%）。我们的结果表明，与安慰剂相比，COMT基因型可能会调节活性透皮尼古丁贴剂的效果，Met/Val或Val/Val基因型个体的尼古丁替代疗法相对益处降低。我们的数据符合一种新出现的结果模式，即多巴胺途径中的基因变异可能为定制戒烟疗法提供未来基础，但表明影响该途径不同成分的不同基因对戒烟药物治疗反应可能有不同影响。
