Smoking Cessation Pharmacotherapy Based on Genetically-Informed Biomarkers: What is the Evidence?
Smoking Cessation Pharmacotherapy Based on Genetically-Informed Biomarkers: What is the Evidence?
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DOI：
10.1093/ntr/ntz009
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发表时间：
2019-09-01
影响因子：
4.7
通讯作者：
David, Sean P.
中科院分区：
文献类型：
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作者：
Panagiotou, Orestis A.;Schuit, Ewoud;David, Sean P.
药物基因组学研究已经使用遗传变异来识别吸烟者可能对戒烟药物治疗有反应。方法：我们对戒烟药物治疗试验的主要和次要分析进行了系统回顾和荟萃分析。符合条件的试验具有先验选择的单核苷酸多态性、复制的非单核苷酸多态性和/或尼古丁代谢物比率的数据。我们估计基因型与治疗的相互作用为不同基因型组治疗效果的风险比（RRR）。结果：我们确定了18项试验（N = 9017名受试者），包括40项活性（安非他酮、尼古丁替代疗法[NRT]、伐尼克兰或联合疗法）与安慰剂比较，16项活性与活性比较。在非西班牙裔黑人吸烟者的6个月戒烟和治疗结束戒烟以及非西班牙裔白人吸烟者的治疗结束戒烟方面，CHRNA5的rs16969968基因型存在统计学上的异质性。rs1051730基因型CHRNA3在非西班牙裔白人吸烟者治疗结束戒烟方面也存在异质性。其他基因型治疗组合没有明确的统计证据。与安慰剂相比，在rs16969968-GG的非西班牙裔黑人吸烟者中，NRT在6个月的戒断（GG vs. GA或AA的RRR， 3.51； 95%可信区间[CI] = 1.19至10.30）和治疗结束戒断（GG vs. GA或AA的RRR， 5.84; 95% CI = 1.89至18.10）方面更有效。在非西班牙裔白人吸烟者中，rs1051730和rs169969960基因型的NRT有效性相对于安慰剂具有可比性。结论：我们没有发现基于基因型的戒烟药物治疗的广泛差异效应。证据的质量一般是中等的。
Introduction: Pharmacogenomic studies have used genetic variants to identify smokers likely to respond to pharmacological treatments for smoking cessation.Methods: We performed a systematic review and meta-analysis of primary and secondary analyses of trials of smoking cessation pharmacotherapies. Eligible were trials with data on a priori selected single nucleotide polymorphisms, replicated non-single nucleotide polymorphisms, and/or the nicotine metabolite ratio. We estimated the genotype x treatment interaction as the ratio of risk ratios (RRR) for treatment effects across genotype groups.Results: We identified 18 trials (N = 9017 participants), including 40 active (bupropion, nicotine replacement therapy [NRT], varenicline, or combination therapies) versus placebo comparisons and 16 active versus active comparisons. There was statistical evidence of heterogeneity across rs16969968 genotypes in CHRNA5 with regard to both 6-month abstinence and end-of-treatment abstinence in non-Hispanic black smokers and end-of-treatment abstinence in non-Hispanic white smokers. There was also heterogeneity across rs1051730 genotypes in CHRNA3 with regard to end-of-treatment abstinence in non-Hispanic white smokers. There was no clear statistical evidence for other genotype-by-treatment combinations. Compared with placebo, NRT was more effective among non-Hispanic black smokers with rs16969968-GG with regard to both 6-month abstinence (RRR for GG vs. GA or AA, 3.51; 95% confidence interval [CI] = 1.19 to 10.30) and end-of-treatment abstinence (RRR for GG vs. GA or AA, 5.84; 95% CI = 1.89 to 18.10). Among non-Hispanic white smokers, NRT effectiveness relative to placebo was comparable across rs1051730 and rs169969960 genotypes.Conclusions: We did not identify widespread differential effects of smoking cessation pharmacotherapies based on genotype. The quality of the evidence is generally moderate.