Functional variant in the DRD2 receptor promoter region and subtypes of alcoholism

Dopaminergic pathway genes are considered as candidate genes for several ne uropsychiatric diseases including severe alcoholism. Since 1990, there have been numerous reports of conflicting association studies of the Tag I A al lele of the dopamine D2 receptor (DRD2) gene and alcoholism. Functional and structural variations in candidate genes offer more direct evaluation of t heir role in the development of a disorder. To determine the role of such v ariations in the DRD2 gene in the development of alcoholism subtypes, we sc reened a sample of 173 alcoholics and 88 normal controls with the A-241G an d -141C Ins/Del variations in the promotor region and C311G variation in ex on 7 of the DRD2 gene. Comparison of alcoholics with normal controls for al lele frequency differences of these three variations was negative. Allele f requency differences of the two variations in the promoter region between t ype II alcoholics, alcoholics with medical complications, and normal contro ls were not significant. There was linkage disequilibrium only between -141 Ins/Del and Tag I D polymorphisms. We conclude that the functional and str uctural variations in DRD2 gene do not play a major role in the development of alcoholism subtypes in our sample. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 96:407-411, 2000. (C) 2000 Wiley-Liss, Inc.