An evaluation of μ-opioid receptor (OPRM1) as a predictor of naltrexone response in the treatment of alcohol dependence
An evaluation of μ-opioid receptor (OPRM1) as a predictor of naltrexone response in the treatment of alcohol dependence
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DOI：
10.1001/archpsyc.65.2.135
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发表时间：
2008-02-01
影响因子：
--
通讯作者：
Goldman, David
中科院分区：
文献类型：
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作者：
Anton, Raymond F.;Oroszi, Gabor;Goldman, David
背景：盐酸纳洛酮治疗酒精依赖对某些人有效，但并不适用于所有人。μ阿片受体基因（OPRM 1）Asn 40 Asp多态性可预测纳洛酮的疗效。目的：探讨酒精中毒患者中是否存在杂合子（Asp 40/Asn 40）或纯合子（Asp 40/Asp 40）的OPRM 1 Asp 40等位基因对纳洛酮的反应更好。设计：药物遗传学分析在2001年1月1日至2004年1月31日之间进行。参与者：符合以下所有3个条件的最近戒酒的志愿者：（1）DSM-IV初级酒精依赖标准;（2）参与联合收割机研究;和（3）DNA的可用性。干预措施：酒精中毒者用100毫克盐酸纳曲酮治疗16周（234例Asn 40纯合子和67例至少有1个Asp 40等位基因拷贝）或安慰剂（235例Asn 40纯合子和68例至少有1个Asp 40等位基因拷贝）。所有参与者接受单独的医疗管理（MM）或联合行为干预（CBI）。主要结果Measures：戒酒天数百分比的时间趋势，大量饮酒天数的百分比，以及良好临床结局的比率。07)重度饮酒天数百分比下降（P=. 04)如果用纳洛酮与安慰剂治疗，而那些Asn 40/Asn 40基因型的人没有表现出药物差异。如果单独使用MM和纳洛酮治疗，87.1%的Asp 40携带者具有良好的临床结局，而Asn 40/Asn 40基因型个体仅为54.8%（优势比，5.75;置信区间，1.88-17.54），而如果用安慰剂治疗，48.6%的Asp 40携带者和54.0%的Asn 40/Asn 40基因型个体具有良好的临床结局（药物和基因型之间的相互作用，P=. 005）。没有基因X药物相互作用中观察到的治疗MM和CBI.Conclusions：这些结果证实和扩展观察功能显着OPRM 1 Asp 40等位基因预测纳洛酮治疗反应在酒精中毒的个人。然而，这种关系可能会被其他有效的治疗方法所掩盖。OPRM 1基因分型在酒精中毒患者中可能有助于选择治疗方案。政府标识符：NCT 00006206。
Context: Naltrexone hydrochloride treatment for alcohol dependence works for some individuals but not for everyone. Asn40Asp, a functional polymorphism of the mu-opioid receptor gene (OPRM1), might predict naltrexone response.Objective: To evaluate whether individuals with alcoholism who are heterozygous (Asp40/Asn40) or homozygous (Asp40/Asp40) for the OPRM1 Asp40 allele respond better to naltrexone.Design: Pharmacogenetic analysis conducted between January 1, 2001, and January 31, 2004.Setting: Eleven academic sites in the COMBINE Study.Participants: Recently abstinent volunteers who met all 3 of the following conditions: (1) DSM-IV criteria for primary alcohol dependence; (2) participation in the COMBINE Study; and (3) availability of DNA.Interventions: Alcoholic subjects were treated for 16 weeks with 100 mg of naltrexone hydrochloride (234 Asn40 homozygotes and 67 with at least 1 copy of the Asp40 allele) or placebo (235 Asn40 homozygotes and 68 with at least 1 copy of the Asp40 allele). All participants received medical management (MM) alone or with combined behavioral intervention (CBI).Main Outcome Measures: Time trends in percentage of days abstinent, percentage of heavy drinking days, and rates of good clinical outcome.Results: Alcoholic subjects with an Asp40 allele receiving MM alone (no CBI) had an increased percentage of days abstinent (P=. 07) and a decreased percentage of heavy drinking days (P=. 04) if treated with naltrexone vs placebo, while those with the Asn40/Asn40 genotype showed no medication differences. If treated with MM alone and naltrexone, 87.1% of Asp40 carriers had a good clinical outcome, compared with only 54.8% of individuals with the Asn40/Asn40 genotype (odds ratio, 5.75; confidence interval, 1.88-17.54), while, if treated with placebo, 48.6% of Asp40 carriers and 54.0% of individuals with the Asn40/Asn40 genotype had a good clinical outcome (interaction between medication and genotype, P=. 005). No gene X medication interactions were observed in those treated with both MM and CBI.Conclusions: These results confirm and extend the observation that the functionally significant OPRM1 Asp40 allele predicts naltrexone treatment response in alcoholic individuals. This relationship might be obscured, however, by other efficacious treatments. OPRM1 geno-typing in alcoholic individuals might be useful to assist in selecting treatment options.Trial Registration: clinicaltrials. gov Identifier: NCT00006206.