Department of Pharmacology and Toxicology, University of Toronto, Toronto, Ontario, Canada.
Department of Preventive Medicine and Public Health, University of Kansas School of Medicine, Kansas City, Kansas, USA.
Clin Pharmacol Ther. 2014 Aug;96(2):256-65. doi: 10.1038/clpt.2014.88. Epub 2014 Apr 14.
Associations between CHRNA5-A3-B4 variants and smoking behaviors exist; however, the association with smoking abstinence is less understood, particularly that among African Americans. In 1,295 African Americans enrolled in two clinical trials, we investigated the association between CHRNA5-A3-B4 and smoking abstinence. The rs2056527(A) allele was associated with lower abstinence with active pharmacotherapy (during treatment: odds ratio (OR) = 0.42, P < 0.001; end of treatment (EOT): OR = 0.55, P = 0.004), or with nicotine gum alone (during treatment: OR = 0.31, P < 0.001; EOT: OR = 0.51, P = 0.02), but not significantly with bupropion, although similar directions and magnitudes were observed (during treatment: OR = 0.54, P = 0.05; EOT: OR = 0.59, P = 0.08). In addition, the rs588765(T) allele was associated with abstinence with gum during treatment (OR = 2.31, P < 0.01). The SNP rs16969968 occurred at a low frequency and was not consistently associated with abstinence. CHRNA5-A3-B4 variants were not associated with tobacco consumption, and adjustments for smoking behaviors did not alter the associations with smoking abstinence. Together, our data suggest that among African Americans, CHRNA5-A3-B4 variants are not associated with baseline smoking but can influence smoking abstinence during active pharmacotherapy.
CHRNA5-A3-B4 变体与吸烟行为之间存在关联;然而,与戒烟的关联则不太为人所知,尤其是在非裔美国人中。在两项临床试验中,共有 1295 名非裔美国人参与,我们调查了 CHRNA5-A3-B4 与戒烟之间的关联。rs2056527(A)等位基因与积极药物治疗期间的较低戒烟率相关(治疗期间:优势比 (OR) = 0.42,P < 0.001;治疗结束时:OR = 0.55,P = 0.004),或与尼古丁口香糖单独使用时的较低戒烟率相关(治疗期间:OR = 0.31,P < 0.001;治疗结束时:OR = 0.51,P = 0.02),但与安非他酮的相关性不显著,尽管观察到了类似的方向和幅度(治疗期间:OR = 0.54,P = 0.05;治疗结束时:OR = 0.59,P = 0.08)。此外,rs588765(T)等位基因与治疗期间使用口香糖的戒烟相关(OR = 2.31,P < 0.01)。SNP rs16969968 发生频率较低,与戒烟率之间没有一致性关联。CHRNA5-A3-B4 变体与吸烟量无关,而且对吸烟行为的调整并没有改变与戒烟的关联。总之,我们的数据表明,在非裔美国人中,CHRNA5-A3-B4 变体与基线吸烟无关,但可以影响积极药物治疗期间的戒烟。