title: Human mu-opioid receptor variation and alcohol dependence.
abstract: Mu-Opioid receptor-mediated neurotransmission is involved in the reward, tolerance, and withdrawal effects of alcohol. The present association study tested the hypothesis that the common Asn40Asp substitution polymorphism in the N-terminal domain of the human mu-opioid receptor (OPRM) confers vulnerability to subtypes of alcohol dependence. The genotypes of the Asn40Asp substitution polymorphism were assessed in 327 German alcohol-dependent subjects (according to ICD-10) and in 340 control subjects of German descent, using an assay based on allele-specific polymerase chain reaction. To select alcoholics with a presumed high genetic load, three subgroups were delineated, marked by (1) a family history of parental alcoholism (n = 114); (2) the inability to abstain from alcohol before the age of 26 years (n = 73); and (3) a history of alcohol withdrawal seizure or delirium (n = 107). The frequency of the Asp40 allele did not differ significantly between the controls [f(Asp40) = 0.078] and either the entire group of alcoholics [f(Asp40) = 0.107; p = 0.066], or the alcoholics with parental alcoholism [f(Asp40) = 0.114; p = 0.094], or the early-onset alcoholics [f(Asp40) = 0.096; p = 0.471,[ or the alcoholics with severe withdrawal symptoms [f(Asp40) = 0.098; p = 0.350]. Our results do not provide evidence that the common Asn40Asp substitution polymorphism of the OPRM gene contributes a major effect to the pathogenesis of alcohol dependence.
authors.affiliation: Department of Psychiatry, University Hospital Benjamin Franklin, Free University of Berlin, Germany.
authors.forename: T
authors.initials: T
authors.lastname: Sander
authors.forename: N
authors.initials: N
authors.lastname: Gscheidel
authors.forename: B
authors.initials: B
authors.lastname: Wendel
authors.forename: J
authors.initials: J
authors.lastname: Samochowiec
authors.forename: M
authors.initials: M
authors.lastname: Smolka
authors.forename: H
authors.initials: H
authors.lastname: Rommelspacher
authors.forename: L G
authors.initials: LG
authors.lastname: Schmidt
authors.forename: M R
authors.initials: MR
authors.lastname: Hoehe
mesh_terms: D000328:Adult; D000430:Alcohol Withdrawal Delirium / Q000235:genetics / Q000534:rehabilitation; D000437:Alcoholism / Q000235:genetics* / Q000534:rehabilitation; D000483:Alleles; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D005828:Genetics, Population; D005838:Genotype; D005858:Germany; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics; D017450:Receptors, Opioid, mu / Q000235:genetics*; D012307:Risk Factors
chemical_list: D017450:Receptors, Opioid, mu