Human mu-opioid receptor variation and alcohol dependence

mu-Opioid receptor-mediated neurotransmission is involved in the reward, to lerance, and withdrawal effects of alcohol, The present association study t ested the hypothesis that the common Asn40Asp substitution polymorphism in the N-terminal domain of the human mu-opioid receptor (OPRM) confers vulner ability to subtypes of alcohol dependence, The genotypes of the Asn40Asp su bstitution polymorphism were assessed in 327 German alcohol-dependent subje cts (according to ICD-10) and in 340 control subjects of German descent, us ing an assay based on allele-specific polymerase chain reaction, To select alcoholics with a presumed high genetic load, three subgroups were delineat ed, marked by (1) a family history of parental alcoholism (n = 114); (2) th e inability to abstain from alcohol before the age of 26 years (n = 73); an d (3) a history of alcohol withdrawal seizure or delirium (n = 107), The fr equency of the Asp40 allele did not differ significantly between the contro ls [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 = 0.4 71] or the alcoholics with severe withdrawal symptoms [f(Asp40) = 0.098; p = 0.350], Our results do not provide evidence that the common Asn40Asp subs titution polymorphism of the OPRM gene contributes a major effect to the pa thogenesis of alcohol dependence.