title: A functional polymorphism of the mu-opioid receptor gene is associated with naltrexone response in alcohol-dependent patients.
abstract: This study examined the association between two specific polymorphisms of the gene encoding the mu-opioid receptor and treatment outcomes in alcohol-dependent patients who were prescribed naltrexone or placebo. A total of 82 patients (71 of European descent) who were randomized to naltrexone and 59 who were randomized to placebo (all of European descent) in one of three randomized, placebo-controlled clinical trials of naltrexone were genotyped at the A(+118)G (Asn40Asp) and C(+17)T (Ala6Val) SNPs in the gene encoding the mu-opioid receptor (OPRM1). The association between genotype and drinking outcomes was measured over 12 weeks of treatment. In subjects of European descent, individuals with one or two copies of the Asp40 allele treated with naltrexone had significantly lower rates of relapse (p=0.044) and a longer time to return to heavy drinking (p=0.040) than those homozygous for the Asn40 allele. There were no differences in overall abstinence rates (p=0.611), nor were there differences in relapse rates or abstinence rates between the two genotype groups among those assigned to placebo. These preliminary results are consistent with prior literature demonstrating that the opioid system is involved in the reinforcing properties of alcohol and that allelic variation at OPRM1 is associated with differential response to a mu-receptor antagonist. If replicated, these results would help to identify alcohol-dependent individuals who may be most likely to respond to treatment with naltrexone.
authors.affiliation: Center for the Study of Addictions, Department of Psychiatry, University of Pennsylvania, 3535 Market Street, Room 3002, Philadelphia, PA 19104, USA. oslin@mail.med.upenn.edu
authors.forename: David W
authors.initials: DW
authors.lastname: Oslin
authors.forename: Wade
authors.initials: W
authors.lastname: Berrettini
authors.forename: Henry R
authors.initials: HR
authors.lastname: Kranzler
authors.forename: Helen
authors.initials: H
authors.lastname: Pettinati
authors.forename: Joel
authors.initials: J
authors.lastname: Gelernter
authors.forename: Joseph R
authors.initials: JR
authors.lastname: Volpicelli
authors.forename: Charles P
authors.initials: CP
authors.lastname: O'Brien
mesh_terms: D000328:Adult; D000437:Alcoholism / Q000188:drug therapy* / Q000235:genetics*; D016001:Confidence Intervals; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D009271:Naltrexone / Q000494:pharmacology / Q000627:therapeutic use*; D016017:Odds Ratio; D011110:Polymorphism, Genetic / Q000502:physiology*; D017450:Receptors, Opioid, mu / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000502:physiology; D016019:Survival Analysis
chemical_list: D017450:Receptors, Opioid, mu; D009271:Naltrexone