title: Increased attributable risk related to a functional mu-opioid receptor gene polymorphism in association with alcohol dependence in central Sweden.
abstract: The mu-opioid receptor (MOR), through its effects on reward and stress-responsivity, modulates alcohol intake in both animal and human laboratory studies. We have previously demonstrated that the frequently occurring A118G single-nucleotide polymorphism (SNP) in exon 1 of the MORgene (OPRM1), which encodes an amino-acid substitution, is functional and receptors encoded by the variant 118G allele bind the endogenous opioid peptide beta-endorphin with three-fold greater affinity than prototype receptors. Other groups subsequently reported that this variant alters stress-responsivity in normal volunteers and also increases the therapeutic response to naltrexone (a mu-preferring opioid antagonist) in the treatment of alcohol dependence. We compared frequencies of genotypes containing an 118G allele in 389 alcohol-dependent individuals and 170 population-based controls without drug or alcohol abuse or dependence. The A118G SNP was present in the Hardy-Weinberg equilibrium with an overall frequency of the 118G allele of 10.9%. There was a significant overall association between genotypes with an 118G allele and alcohol dependence (p=0.0074). The attributable risk for alcohol dependence in subjects with an 118G allele was 11.1%. There was no difference in A118G genotype between type 1 and type 2 alcoholics. In central Sweden, the functional variant 118G allele in exon 1 of OPRM1 is associated with an increased attributable risk for alcohol dependence.
authors.affiliation: The Laboratory of the Biology of Addictive Diseases, The Rockefeller University, New York, NY 10021, USA. bartg@rockefeller.edu
authors.forename: Gavin
authors.initials: G
authors.lastname: Bart
authors.forename: Mary Jeanne
authors.initials: MJ
authors.lastname: Kreek
authors.forename: Jurg
authors.initials: J
authors.lastname: Ott
authors.forename: K Steven
authors.initials: KS
authors.lastname: LaForge
authors.forename: Dmitri
authors.initials: D
authors.lastname: Proudnikov
authors.forename: Lotta
authors.initials: L
authors.lastname: Pollak
authors.forename: Markus
authors.initials: M
authors.lastname: Heilig
mesh_terms: D000328:Adult; D000368:Aged; D000437:Alcoholism / Q000453:epidemiology / Q000235:genetics* / Q000523:psychology; D005006:Ethnicity; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics*; D011569:Psychiatric Status Rating Scales; D017450:Receptors, Opioid, mu / Q000235:genetics*; D018570:Risk Assessment; D013548:Sweden / Q000453:epidemiology
chemical_list: D017450:Receptors, Opioid, mu