Mental Illness Research, Education and Clinical Center, Philadelphia, PA, USA.
Center for Studies of Addiction, Department of Psychiatry, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.
Addiction. 2020 Aug;115(8):1426-1437. doi: 10.1111/add.14975. Epub 2020 Feb 11.
There is wide inter-individual variability in response to the treatment of alcohol use disorder (AUD) with the opioid receptor antagonist naltrexone. To identify patients who may be most responsive to naltrexone treatment, studies have examined the moderating effect of rs1799971, a single nucleotide polymorphism (SNP) that encodes a non-synonymous substitution (Asn40Asp) in the mu-opioid receptor gene, OPRM1. The aims of this study were to: (1) conduct a systematic review of randomized clinical trials (RCTs); (2) assess the bias of the available studies and gauge publication bias; and (3) meta-analyze the interaction effect of the Asn40Asp SNP on the response to naltrexone treatment.
We searched for placebo-controlled RCTs that examined the effect of Asn40Asp on the response to naltrexone treatment of heavy drinking or AUD. We tested the hypothesis that the minor (Asp40) allele was associated with a greater reduction in five alcohol consumption measures (relapse to heavy drinking, abstinence, percentage of heavy drinking days, percentage of days abstinent and drinks per day) in naltrexone-treated participants by meta-analyzing the interaction effects using a random effects model.
Seven RCTs met the study criteria. Overall, risk of bias was low and we observed no evidence of publication bias. Of the five alcohol consumption outcomes considered, there was a nominally significant moderating effect of the Asn40Asp SNP only on drinks per day (d = -0.18, P = 0.02). However, the effect was not significant when multiple comparisons were taken into account.
From the evidence to date, it remains unclear whether rs1799971, the OPRM1 Asn40Asp single nucleotide polymorphism, predicts naltrexone treatment response in individuals with alcohol use disorder or heavy drinking.
阿片受体拮抗剂纳曲酮治疗酒精使用障碍（AUD）的个体反应存在广泛的个体间差异。为了确定可能对纳曲酮治疗最敏感的患者，研究已经检查了 rs1799971 的调节作用，rs1799971 是编码 μ-阿片受体基因（OPRM1）中一个非同义取代（Asn40Asp）的单核苷酸多态性（SNP）。本研究的目的是：（1）进行系统评价随机临床试验（RCT）；（2）评估现有研究的偏倚并评估发表偏倚；（3）对 Asn40Asp SNP 对纳曲酮治疗反应的交互作用进行荟萃分析。
我们搜索了安慰剂对照 RCT，以检查 Asn40Asp 对纳曲酮治疗重度饮酒或 AUD 反应的影响。我们通过使用随机效应模型对交互作用进行荟萃分析，检验了次要（Asp40）等位基因与纳曲酮治疗参与者中五种饮酒量测量（重度饮酒复发、戒酒、重度饮酒天数百分比、戒酒天数百分比和每天饮酒量）减少量更大的假设。
有 7 项 RCT 符合研究标准。总体而言，偏倚风险较低，我们没有发现发表偏倚的证据。在所考虑的五个饮酒量结果中，只有 Asn40Asp SNP 对每天饮酒量的调节作用具有名义显著性（d=-0.18，P=0.02）。但是，当考虑到多次比较时，该效果并不显著。
根据目前的证据，rs1799971（OPRM1 Asn40Asp 单核苷酸多态性）是否可预测酒精使用障碍或重度饮酒者对纳曲酮治疗的反应仍不清楚。
