title: An intronic variant in OPRD1 predicts treatment outcome for opioid dependence in African-Americans.
abstract: 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.
authors.affiliation: Center for Neurobiology and Behavior, Department of Psychiatry, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA. crist@mail.med.upenn.edu
authors.forename: Richard C
authors.initials: RC
authors.lastname: Crist
authors.forename: Toni-Kim
authors.initials: TK
authors.lastname: Clarke
authors.forename: Alfonso
authors.initials: A
authors.lastname: Ang
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Ambrose-Lanci
authors.forename: Falk W
authors.initials: FW
authors.lastname: Lohoff
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Saxon
authors.forename: Walter
authors.initials: W
authors.lastname: Ling
authors.forename: Maureen P
authors.initials: MP
authors.lastname: Hillhouse
authors.forename: R Douglas
authors.initials: RD
authors.lastname: Bruce
authors.forename: George
authors.initials: G
authors.lastname: Woody
authors.forename: Wade H
authors.initials: WH
authors.lastname: Berrettini
mesh_terms: D000328:Adult; D001741:Black or African American / Q000235:genetics*; D000701:Analgesics, Opioid / Q000627:therapeutic use / Q000652:urine; D002047:Buprenorphine / Q000627:therapeutic use*; D000069479:Buprenorphine, Naloxone Drug Combination; D005260:Female; D005838:Genotype; D006801:Humans; D007438:Introns / Q000235:genetics; D008297:Male; D008691:Methadone / Q000627:therapeutic use*; D008875:Middle Aged; D009270:Naloxone / Q000627:therapeutic use*; D009292:Narcotic Antagonists / Q000627:therapeutic use; D009294:Narcotics / Q000627:therapeutic use; D009293:Opioid-Related Disorders / Q000188:drug therapy / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D017465:Receptors, Opioid, delta / Q000235:genetics*; D016896:Treatment Outcome; D044465:White People / Q000235:genetics
chemical_list: D000701:Analgesics, Opioid; D000069479:Buprenorphine, Naloxone Drug Combination; D009292:Narcotic Antagonists; D009294:Narcotics; C529706:OPRD1 protein, human; D017465:Receptors, Opioid, delta; D009270:Naloxone; D002047:Buprenorphine; D008691:Methadone