Bress Adam, Kittles Rick, Wing Coady, Hooker Stanley E, King Andrea
aDepartment of Pharmacotherapy, University of Utah, Salt Lake City, Utah bDepartment of Surgery, University of Arizona, Tuscon, Arizona cSchool of Public and Environmental Affairs, Indiana University, Bloomington, Indiana dDepartment of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas eDepartment of Psychiatry and Behavioral Neuroscience, University of Chicago, Chicago, Illinois, USA.
Pharmacogenet Genomics. 2015 Jun;25(6):305-12. doi: 10.1097/FPC.0000000000000138.
To determine whether there were differential quit rates between African Americans (AA) and European Americans with the experimental treatment naltrexone, and examine the role of genetic ancestry on these outcomes among AAs.
Data from a previous randomized trial of 315 smokers to naltrexone versus placebo were reanalyzed using West African (WA) genetic ancestry to define subpopulations. Logistic regression models were used to estimate treatment effects on early and end of treatment quit rates, by race and WA ancestry.
Among European Americans (n=136), naltrexone significantly increased quit rates at 4 weeks (62 vs. 43%, P=0.03) with directional, but not statistically significant effects at 12 weeks (30 vs. 18%, P=0.12). In contrast, among the AAs (n=95), quit rates did not differ between naltrexone and placebo groups at either interval (4 weeks: 43 vs. 32%, P=0.27; 12 weeks: 22 vs. 18%, P=0.60). A median split was conducted in AAs for WA ancestry. Among AAs with low WA ancestry, quit rates were significantly higher with naltrexone compared with placebo (60 vs. 27%, P=0.03). There was no advantage in quit rates with naltrexone for the high WA ancestry group.
Naltrexone efficacy for smoking cessation varies across AA individuals with different levels of WA ancestry. These results suggest that genetic background may partially explain racial differences in drug response.
确定接受实验性治疗纳曲酮的非裔美国人（AA）和欧裔美国人之间的戒烟率是否存在差异，并研究基因血统在非裔美国人这些结果中的作用。
使用西非（WA）基因血统来定义亚群，对先前一项针对315名吸烟者进行纳曲酮与安慰剂对比的随机试验数据进行重新分析。采用逻辑回归模型，按种族和WA血统估计治疗对治疗早期和结束时戒烟率的影响。
在欧裔美国人（n = 136）中，纳曲酮在4周时显著提高了戒烟率（62%对43%，P = 0.03），在12周时有方向性但无统计学显著影响（30%对18%，P = 0.12）。相比之下，在非裔美国人（n = 95）中，纳曲酮组和安慰剂组在两个时间段的戒烟率均无差异（4周：43%对32%，P = 0.27；12周：22%对18%，P = 0.60）。对非裔美国人按WA血统进行中位数分割。在WA血统低的非裔美国人中，与安慰剂相比，纳曲酮组的戒烟率显著更高（60%对27%，P = 0.03）。WA血统高的组使用纳曲酮在戒烟率上没有优势。
纳曲酮在戒烟方面的疗效因WA血统水平不同的非裔美国人个体而异。这些结果表明基因背景可能部分解释了药物反应中的种族差异。
