Genetic polymorphisms and response to medications for alcohol use disorders: a systematic review and meta-analysis

Pharmacogenomics. 2014 Sep;15(13):1687-700. doi: 10.2217/pgs.14.121.

Abstract

Aim: To assess whether response to medications for alcohol use disorders varies by genotype.

Methods: Systematic review and meta-analysis.

Results: We found no studies that assessed the clinical utility of genotype-guided dosing strategies or genotype-guided medication selection, and none randomized by genotype. All included studies assessed the association between genotype and response to medication. Of 15 included studies, eight (n = 1365 participants) assessed variation in naltrexone response and polymorphisms of OPRM1. Our meta-analyses for return to heavy drinking found no significant difference between A allele homozygotes and those with at least one G allele, both without (risk difference: 0.26; 95% CI: -0.01-0.53; n = 174) and with inclusion of studies rated as high or unclear risk of bias (risk difference: 0.14; 95% CI: -0.03-0.3; n = 382). For all other polymorphism-medication pairs, we found just one eligible study.

Conclusion: Estimates of effect for return to heavy drinking suggest it is possible that patients with at least one G allele of A118G polymorphism of OPRM1 might be more likely to respond to naltrexone, but confidence intervals were wide; additional studies are needed to improve confidence in the estimates.

Keywords: OPRM1; alcohol; alcohol dependence; alcohol use disorder; naltrexone; opioid receptor; pharmacogenomics; polymorphism; systematic review.

Publication types

  • Meta-Analysis
  • Research Support, U.S. Gov't, P.H.S.
  • Review
  • Systematic Review

MeSH terms

  • Alcohol-Induced Disorders / drug therapy
  • Alcohol-Induced Disorders / genetics*
  • Genotype
  • Humans
  • Naltrexone / therapeutic use
  • Polymorphism, Genetic*
  • Receptors, Opioid, mu / genetics

Substances

  • OPRM1 protein, human
  • Receptors, Opioid, mu
  • Naltrexone