Genetic predisposition in alcoholism: association of the D2 dopamine receptor TaqI B1 RFLP with severe alcoholics.

Previous studies have shown an association of the 3' Taq1 A1 allele of the D2 dopamine receptor (DRD2) gene with severe alcoholism. The recent demonstration of a new polymorphism located closer to the regulatory regions of this gene, permits an associational analysis of these 5' Taq1 B alleles with alcoholism and a comparison with the 3' Taq1 A alleles. Restriction fragment length polymorphism methodology was used to analyze a total of 133 blood samples of nonalcoholics, less severe alcoholics, and severe alcoholics. In white subjects (n = 115), no significant difference in the prevalence of the B1 allele is found between nonalcoholics (n = 30) and less severe alcoholics (n = 36). However, the prevalence of this allele is significantly higher in severe alcoholics (n = 49) when compared to either nonalcoholics (p = 0.008) or less severe alcoholics (p = 0.005). When Taq1 B and Taq1 A alleles of the DRD2 gene are compared in whites, the prevalence of the A1 allele is significantly higher than the B1 allele only in the severe alcoholic group. In conclusion, alleles in both the 5' and 3' region of the DRD2 gene associate with severe alcoholism. This suggests that the DRD2 gene may have an etiological role in some severe alcoholics.

Association of the A1 allele of the D2 dopamine receptor gene with severe alcoholism.

In a blinded study, 159 subjects composed of nonalcoholics (N = 43), less severe alcoholics (N = 44), severe alcoholics (N = 52) and young children of alcoholics (CoAs, N = 20) were studied for their allelic association with the D2 dopamine receptor (D2DR) gene utilizing peripheral lymphocytes as the DNA source. The combined alcoholic group compared to the nonalcoholic group showed a significantly greater association with the A1 allele of the D2DR gene. Furthermore, an even more robust association was found when severe alcoholics were compared to nonalcoholics. CoAs also showed a significantly greater association with the A1 allele than nonalcoholics but not when compared to alcoholics. Analysis of risk of alcoholism severity suggests that it comprises of two independent components: family history of alcoholism and presence of the A1 allele. Genotype and allelic frequency of the D2DR gene were also analyzed with respect to race. A higher percentage of blacks compared to whites had the A1/A1 genotype, and A1 allelic frequency in the total sample of blacks was significantly greater than in the total sample of whites. Moreover, frequency of the A1 allele was significantly greater in severe alcoholics compared to nonalcoholics in both whites and blacks. However, due to the small sample size of blacks, these racial differences need to be further studied. This study, of the largest sample of alcoholics to date, strongly affirms association of severe alcoholism with the A1 allele of the D2DR gene.