title: Genetic variation in OPRD1 and the response to treatment for opioid dependence with buprenorphine in European-American females.
abstract: Two commonly prescribed treatments for opioid addiction are methadone and buprenorphine. Although these drugs show some efficacy in treating opioid dependence, treatment response varies among individuals. It is likely that genetic factors have a role in determining treatment outcome. This study analyses the pharmacogenetic association of six polymorphisms in OPRD1, the gene encoding the delta-opioid receptor, on treatment outcome in 582 opioid addicted European Americans randomized to either methadone or buprenorphine/naloxone (Suboxone) over the course of a 24-week open-label clinical trial. Treatment outcome was assessed as the number of missed or opioid-positive urine drug screens over the 24 weeks. In the total sample, no single-nucleotide polymorphisms (SNPs) in OPRD1 were significantly associated with treatment outcome in either treatment arm. However, sex-specific analyses revealed two intronic SNPs (rs581111 and rs529520) that predicted treatment outcome in females treated with buprenorphine. Females with the AA or AG genotypes at rs581111 had significantly worse outcomes than those with the GG genotype when treated with buprenorphine (P=0.03, relative risk (RR)=1.67, 95% confidence interval (CI) 1.06-2.1). For rs529520, females with the AA genotype had a significantly worse outcome than those with the CC genotype when (P=0.006, RR=2.15, 95% CI 1.3-2.29). No significant associations were detected in males. These findings suggest that rs581111 and rs52920 may be useful when considering treatment options for female opioid addicts, however, confirmation in an independent sample is warranted.
authors.affiliation: Department of Psychiatry, Center for Neurobiology and Behavior, Translational Research Laboratories, University of Pennsylvania School of Medicine, Philadelphia, PA, USA.
authors.forename: T-K
authors.initials: TK
authors.lastname: Clarke
authors.affiliation: Department of Psychiatry, Center for Neurobiology and Behavior, Translational Research Laboratories, University of Pennsylvania School of Medicine, Philadelphia, PA, USA.
authors.forename: R C
authors.initials: RC
authors.lastname: Crist
authors.affiliation: Integrated Substance Abuse Programs, University of California, Los Angeles, CA, USA.
authors.forename: A
authors.initials: A
authors.lastname: Ang
authors.affiliation: Department of Psychiatry, Center for Neurobiology and Behavior, Translational Research Laboratories, University of Pennsylvania School of Medicine, Philadelphia, PA, USA.
authors.forename: L M
authors.initials: LM
authors.lastname: Ambrose-Lanci
authors.affiliation: Department of Psychiatry, Center for Neurobiology and Behavior, Translational Research Laboratories, University of Pennsylvania School of Medicine, Philadelphia, PA, USA.
authors.forename: F W
authors.initials: FW
authors.lastname: Lohoff
authors.affiliation: Veteran's Affairs Puget Sound Health Care System, Seattle, WA, USA.
authors.forename: A J
authors.initials: AJ
authors.lastname: Saxon
authors.affiliation: Integrated Substance Abuse Programs, University of California, Los Angeles, CA, USA.
authors.forename: W
authors.initials: W
authors.lastname: Ling
authors.affiliation: Integrated Substance Abuse Programs, University of California, Los Angeles, CA, USA.
authors.forename: M P
authors.initials: MP
authors.lastname: Hillhouse
authors.affiliation: Yale University School of Medicine, New Haven, CT, USA.
authors.forename: R D
authors.initials: RD
authors.lastname: Bruce
authors.affiliation: Perelman School of Medicine at the University of Pennsylvania and Treatment Research Institute, Philadelphia, PA, USA.
authors.forename: G
authors.initials: G
authors.lastname: Woody
authors.affiliation: Department of Psychiatry, Center for Neurobiology and Behavior, Translational Research Laboratories, University of Pennsylvania School of Medicine, Philadelphia, PA, USA.
authors.forename: W H
authors.initials: WH
authors.lastname: Berrettini
mesh_terms: D002047:Buprenorphine / Q000627:therapeutic use*; D005260:Female; D014644:Genetic Variation; D006801:Humans; D009293:Opioid-Related Disorders / Q000188:drug therapy* / Q000235:genetics; D017465:Receptors, Opioid, delta / Q000235:genetics*; D044465:White People
chemical_list: C529706:OPRD1 protein, human; D017465:Receptors, Opioid, delta; D002047:Buprenorphine