HUMAN GABA(A) RECEPTOR ALPHA(1) AND ALPHA(3) SUBUNITS GENES AND ALCOHOLISM

gamma-Aminobutyric acid (GABA) is the major inhibitory neurotransmitte r in the brain, GABA effects are largely mediated by binding to the po stsynaptic GABA(A) receptor, causing the opening of an integral chlori de-ion channel, The GABA(A) antagonists picrotoxin and bicuculline red uce some ethanol-induced behaviors, such as motor impairment, sedation , and hypnosis. The role of this receptor in alcoholism is further sup ported by effective alleviation of alcohol withdrawal symptoms by GABA (A) agonists, To determine the role of the GABA(A) receptor (GABR) gen es in the development of alcoholism, we have used alpha(1) and alpha(3 ) simple sequence repeat polymorphisms in a sample of unrelated alcoho lics, alcoholic probands with both parents, and psychiatrically normal controls, For the GABR alpha(1) gene, the differences between allele frequencies, when all alleles were compared together, were not signifi cant between total alcoholics, subtypes of alcoholics, and normal cont rols, However, for GABR alpha(3), the differences between total alcoho lics and normal controls were significant when all alleles were compar ed together, The differences between subtypes of alcoholics and normal controls were not significant, The results of haplotype relative risk analysis for both genes, GABR alpha(1) and GABR alpha(3), were also n egative, It is possible that the sample size in the haplotype relative risk is too small to have power to detect the differences in transmit ted versus nontransmitted alleles, There is a need for a replication s tudy in a large family sample that will allow haplotype relative risk or affected sib-pair analysis.