Opioid Receptor Gene (OPRM1, OPRK1, and OPRD1) Variants and Response to Naltrexone Treatment for Alcohol Dependence: Results From the VA Cooperative Study

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Abstract
Background: Pharmacotherapy of alcohol dependence (AD) is at an early stage of development; currently available medications have limited efficacy. It would be clinically valuable to identify, before initiation of a course of treatment, those patients who, based on genetic markers, are most likely to respond to a specific pharmacotherapy. A previous report suggested that a functional variant at the genetic locus encoding the μ opioid receptor (Asn40Asp) is such a marker, in short‐term (3‐month) treatment with the opioid‐blocking drug naltrexone (NTX). Methods: We studied polymorphic variants at each of the 3 opioid receptor genes—OPRM1, OPRD1, and OPRK1, which encode the μ, δ, and κ opioid receptors, respectively—including the OPRM1 Asn40Asp variant—as predictors of response to NTX or placebo in 215 alcohol‐dependent male subjects who participated in Veterans Affairs Cooperative Study 425, “Naltrexone in the Treatment of Alcohol Dependence.” Results: At the 3‐month time point, treatment condition, age, and the pretreatment number of drinks per drinking day were all significant (pOPRM1 Asn40Asp polymorphism with NTX treatment response for AD.