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An Intronic Variant in OPRD1 Predicts Treatment Outcome for Opioid Dependence in African-Americans.

Neuropsychopharmacology 2013;38:2003-2010. [doi: 10.1038/npp.2013.99]

Richard C. Crist, PhD (University of Pennsylvania), Toni-Kim Clarke, PhD (University of Pennsylvania), Alfonso Ang, PhD (Integrated Substance Abuse Programs, UCLA, PR Node), Lisa M. Ambrose-Lanci, PhD (University of Pennsylvania), Falk W. Lohoff, MD (University of Pennsylvania), Andrew J. Saxon, MD (VA Puget Sound Health Care System, PN Node), Walter Ling, MD (Integrated Substance Abuse Programs, UCLA, PR Node), Maureen Hillhouse, PhD (Integrated Substance Abuse Programs, UCLA, PR Node), R. Douglas Bruce, MD, MA (Yale University School of Medicine, NEC Node), George E. Woody, MD (University of Pennsylvania School of Medicine), Wade H. Berrettini, MD, PhD (University of Pennsylvania).

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 mu-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 (as part of National Drug Abuse Treatment Clinical Trial CTN-0027, "Starting Treatment with Agonist Replacement Therapies (START)"). 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. 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.

Conclusions: 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. (Article (Peer-Reviewed), PDF, English, 2013)

Keywords: African Americans | Buprenorphine/Naloxone | CTN platform/ancillary study | Genetics | Methadone maintenance | Opioid dependence | Pharmacological therapy | Suboxone | Neuropsychopharmacology (journal)

Document No: 977, PMID: 23612435, PMCID: PMC3746708.

Submitted by CTN Dissemination Librarians, 5/15/2013.

Ambrose-Lanci, Lisa search
Ang, Alfonso search
Berrettini, Wade search
Bruce, R. Douglas search mail
Clarke, Toni-Kim search
Crist, Richard C. search mail
Hillhouse, Maureen search mail
Ling, Walter search mail
Lohoff, Falk W. search
Saxon, Andrew J. search mail
Woody, George E. search mail
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