Opioid receptor gene (OPRM1, OPRK1, and OPRD1) variants and response to naltrexone treatment for alcohol dependence: Results from the VA Cooperative Study

Joel Gelernter, Ralitza Gueorguieva, Henry R. Kranzler, Huiping Zhang, Joyce Cramer, Robert Rosenheck, John H. Krystal, K. Drexler, J. Hermos, L. Rugle, O. Kausch, B. Adinoff, J. Grabowski, R. Wancha, L. Madlock, M. FeBornstein, J. Pena, P. Casadonte, S. Nixon, C. ShawL. Haynes-Tucker, L. Moffet, I. Maany, G. Kaplan, C. Stock, P. Banys, A. Saxon, W. Krol, M. Miller

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158 Scopus citations

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 (p<0.05) predictors of the rate of relapse and time to relapse. Although NTX had no significant effect on relapse to heavy drinking in the overall sample in CSP 425, it significantly reduced relapse in the subgroup that provided DNA for analysis (i.e., the present study sample). There were no significant interactions between any individual single nucleotide polymorphisms studied and NTX treatment response. Conclusions: These results do not support association of the OPRM1 Asn40Asp polymorphism with NTX treatment response for AD.

Original languageEnglish (US)
Pages (from-to)555-563
Number of pages9
JournalAlcoholism: Clinical and Experimental Research
Volume31
Issue number4
DOIs
StatePublished - Apr 1 2007

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Keywords

  • Alcohol Dependence Treatment
  • Naltrexone
  • OPRD1
  • OPRK1
  • OPRM1
  • Opioid Receptor Genes
  • Pharmacogenetics

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Toxicology
  • Psychiatry and Mental health

Cite this

Gelernter, J., Gueorguieva, R., Kranzler, H. R., Zhang, H., Cramer, J., Rosenheck, R., Krystal, J. H., Drexler, K., Hermos, J., Rugle, L., Kausch, O., Adinoff, B., Grabowski, J., Wancha, R., Madlock, L., FeBornstein, M., Pena, J., Casadonte, P., Nixon, S., ... Miller, M. (2007). Opioid receptor gene (OPRM1, OPRK1, and OPRD1) variants and response to naltrexone treatment for alcohol dependence: Results from the VA Cooperative Study. Alcoholism: Clinical and Experimental Research, 31(4), 555-563. https://doi.org/10.1111/j.1530-0277.2007.00339.x