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

Dopaminergic pathway genes are considered as candidate genes for several neuropsychiatric diseases including severe alcoholism. Since 1990, there have been numerous reports of conflicting association studies of the Taq I A allele of the dopamine D2 receptor (DRD2) gene and alcoholism. Functional and structural variations in candidate genes offer more direct evaluation of their role in the development of a disorder. To determine the role of such variations in the DRD2 gene in the development of alcoholism subtypes, we screened a sample of 173 alcoholics and 88 normal controls with the A-241G and -141C Ins/Del variations in the promoter region and C311G variation in exon 7 of the DRD2 gene. Comparison of alcoholics with normal controls for allele frequency differences of these three variations was negative. Allele frequency differences of the two variations in the promoter region between type II alcoholics, alcoholics with medical complications, and normal controls were not significant. There was linkage disequilibrium only between -141 Ins/Del and Taq I D polymorphisms. We conclude that the functional and structural variations in DRD2 gene do not play a major role in the development of alcoholism subtypes in our sample.