D-2 dopamine receptor and GABA(A) receptor beta 3 subunit genes and alcoholism

As the dopaminergic and GABAergic systems have been implicated in alcohol-r elated behaviors, variants of the D-2 dopamine receptor (DRD2) and GABA(A) receptor beta 3 subunit (GABRB3) genes were determined;in a population-base d association study of Caucasian non-alcoholic and alcoholic subjects. In s evere alcoholics, compared to non-alcoholics, a significant increase was fo und in the prevalence (P = 1.7 x 10(-5)) and frequency (P = 1.6 x 10(-5)) o f the DRD2 minor (Al) allele. Moreover, a significant progressive increase was observed in Al allelic prevalence (P = 3.1 x 10(-6)) and frequency (P = 2.7 x 10(-6)) in the order of non-alcoholics, less severe and severe alcoh olics. In severe alcoholics, compared to non-alcoholics, a significant decr ease was found in the prevalence (P = 4.5 x 10(-3)) and frequency (P = 2.7 x 10(-2)) of the GABRB3 major (G1) allele. Furthermore, a significant progr essive decrease was noted in GI allelic prevalence (P = 2.4 x 10(-3)) and f requency (P = 1.9 x 10(-2)) in non-alcoholics, less severe and severe alcoh olics, respectively. In sum, in the same population of non-alcoholics and a lcoholics studied, variants of both the DRD2 and GABRB3 genes independently contribute to the risk for alcoholism, with the DRD2 variants revealing a stronger effect than the GABRB3 variants. However, when the DRD2 and the GA BRB3 variants are combined, the risk for alcoholism is more robust than whe n these variants are considered separately. (C) 1998 Elsevier Science Irela nd Ltd. All rights reserved.