Western Psychiatric Institute and Clinic, University of Pittsburgh School of Medicine, 3811 O'Hara Street, Pittsburgh, PA 15213, USA.
Cancer Epidemiol Biomarkers Prev. 2009 Oct;18(10):2608-12. doi: 10.1158/1055-9965.EPI-09-0166. Epub 2009 Sep 15.
Genes coding for nicotinic acetylcholine receptors may influence response to nicotine replacement therapy for smoking cessation. We examined the association of a 3' untranslated region polymorphism (rs2072661) in the nicotinic acetylcholine receptor beta2 subunit (CHRNB2) gene with quitting success in response to nicotine versus placebo patch during a short-term test of patch effects. In a within-subjects cross-over design, smokers of European descent (n = 156) received 21 mg nicotine and placebo patch in counter-balanced order, during two separate 5-day simulated quit attempts, each preceded by a week of ad libitum smoking. Abstinence was assessed daily by CO < 5 ppm. Smokers with the CHRNB2 GG genotype had more days of abstinence during the nicotine versus placebo patch week compared with those with the AG or AA genotypes (P < 0.01). Moreover, nicotine patch increased the probability of quitting on the target quit day, quitting anytime during the patch week, and avoiding relapse among those with the GG genotype but not the AA/AG genotypes, although the nicotine x genotype interaction was significant only for quitting on the target quit day (P < 0.05). Regardless of patch condition, quitting on the target quit day was more likely in those with the GG genotype versus AA/AG genotypes (P < 0.05). Genetic associations were not observed for craving or withdrawal responses to nicotine versus placebo patch. These findings are consistent with previous evidence of association of this variant with smoking cessation and suggest that polymorphisms in the nicotinic acetylcholine receptor beta2 subunit gene may influence therapeutic responsiveness to cessation medications.
编码烟碱型乙酰胆碱受体的基因可能会影响戒烟时尼古丁替代疗法的效果。我们研究了烟碱乙酰胆碱受体β2 亚基（CHRNB2）基因 3'非翻译区多态性（rs2072661）与尼古丁贴片与安慰剂贴片短期疗效试验中戒烟成功的相关性。在一个个体交叉设计中，欧洲裔吸烟者（n=156）在两个单独的 5 天模拟戒烟尝试中，分别以尼古丁和安慰剂贴片顺序进行治疗，每个尝试前有一周的自由吸烟期。通过 CO<5ppm 来评估每日的戒烟情况。与 AG 或 AA 基因型相比，携带 CHRNB2 GG 基因型的吸烟者在尼古丁贴片与安慰剂贴片周期间有更多的戒烟天数（P<0.01）。此外，尼古丁贴片增加了目标戒烟日戒烟的可能性，增加了贴片周期间任何时间戒烟的可能性，以及避免了 GG 基因型但不是 AA/AG 基因型的吸烟者的复吸，尽管尼古丁 x 基因型交互作用仅在目标戒烟日戒烟方面具有统计学意义（P<0.05）。无论贴片条件如何，在目标戒烟日戒烟的可能性在 GG 基因型比 AA/AG 基因型更高（P<0.05）。对于尼古丁与安慰剂贴片之间的渴求或戒断反应，未观察到遗传相关性。这些发现与该变体与戒烟相关的先前证据一致，并表明烟碱型乙酰胆碱受体β2 亚基基因的多态性可能会影响戒烟药物的治疗反应。
