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An intronic variant in OPRD1 predicts treatment outcome for opioid dependence in African-Americans.

Although buprenorphine and methadone are both effective treatments for opioid dependence, their efficacy can vary significantly among patients. Genetic differences may explain some of the variability in treatment outcome. Understanding the interactions between genetic background and pharmacotherapy may result in more informed treatment decisions. This study is a pharmacogenetic analysis of the effects of genetic variants in OPRD1, the gene encoding the δ-opioid receptor, on the prevalence of opioid-positive urine tests in African-Americans (n=77) or European-Americans (n=566) undergoing treatment for opioid dependence. Patients were randomly assigned to treatment with either methadone or buprenorphine/naloxone (Suboxone) over a 24-week open-label clinical trial, in which illicit opioid use was measured by weekly urinalysis. In African-Americans, the intronic SNP rs678849 predicted treatment outcome for both medications. Methadone patients with the CC genotype were less likely to have opioid-positive urine tests than those in the combined CT and TT genotypes group (relative risk (RR)=0.52, 95% confidence interval (CI)=0.44-0.60, p=0.001). In the buprenorphine treatment group, however, individuals with the CC genotype were more likely to have positive opioid drug screens than individuals in the combined CT and TT genotypes group (RR=2.17, 95% CI=1.95-2.68, p=0.008). These findings indicate that the genotype at rs678849 predicts African-American patient response to two common treatments for opioid dependence, suggesting that matching patients to treatment type based on the genotype at this locus may improve overall treatment efficacy. This observation requires confirmation in an independent population.

Pubmed ID: 23612435

Authors

  • Crist RC
  • Clarke TK
  • Ang A
  • Ambrose-Lanci LM
  • Lohoff FW
  • Saxon AJ
  • Ling W
  • Hillhouse MP
  • Bruce RD
  • Woody G
  • Berrettini WH

Journal

Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology

Publication Data

September 16, 2013

Associated Grants

  • Agency: NIDA NIH HHS, Id: P20 DA025995
  • Agency: NIDA NIH HHS, Id: P20DA025995
  • Agency: NIDA NIH HHS, Id: P60 DA005186
  • Agency: NIDA NIH HHS, Id: P60DA05186
  • Agency: NIMH NIH HHS, Id: T32 MH014654
  • Agency: NIMH NIH HHS, Id: T32MH014654
  • Agency: NIDA NIH HHS, Id: U10 DA013036
  • Agency: NIDA NIH HHS, Id: U10 DA013043
  • Agency: NIDA NIH HHS, Id: U10 DA013045
  • Agency: NIDA NIH HHS, Id: U10 DA013046
  • Agency: NIDA NIH HHS, Id: U10 DA013714
  • Agency: NIDA NIH HHS, Id: U10 DA015815
  • Agency: NIDA NIH HHS, Id: U10 DA01714
  • Agency: NIDA NIH HHS, Id: U10 DA13038
  • Agency: NIDA NIH HHS, Id: U10 DA13043
  • Agency: NIDA NIH HHS, Id: U10 DA13045

Mesh Terms

  • Adult
  • African Americans
  • Analgesics, Opioid
  • Buprenorphine
  • European Continental Ancestry Group
  • Female
  • Genotype
  • Humans
  • Introns
  • Male
  • Methadone
  • Middle Aged
  • Naloxone
  • Narcotic Antagonists
  • Narcotics
  • Opioid-Related Disorders
  • Polymorphism, Single Nucleotide
  • Receptors, Opioid, delta
  • Treatment Outcome