Identification of a novel polymorphism of the human dopamine transporter (DAT1) gene and the significant association with alcoholism

Abstract

Human dopamine transporter gene (DAT1) has a variable number of tandem repeats (VNTR) in its 3′-untranslated region (UTR). The association between the VNTR polymorphism and neuropsychiatric disorders has been studied, but their relationship is still unclear. Here we identified a novel polymorphism in the 3′-UTR of the DAT1 gene, G2319A, and a significant association between the polymorphism and alcoholism was observed in both genotypic and allelic frequencies (P = 0.040 and 0.019, extended Fisher's exact test, respectively). There was a significant gene dose effect on the risk for alcoholism associated with the 2319-A allele (χ² = 6.16, df = 2, P = 0.046, linearity tendency test: Cochranq–Armitage analysis). Moreover, in the haplotype analysis with G2319A- and VNTR-polymorphisms, a positive gene dose efffect on the risk with the A10 allele (P = 0.044, linearity tendency test) and a negative gene dose effect with the G10 allele (P = 0.010, linearity tendency test) for alcoholism were significantly detected. Odds ratio for alcoholism with the A10 and G10 alleles were 1.76 (1.12–2.76) and 0.53 (0.32–0.79), respectively. These results indicate that the DAT1 gene may confer vulnerability to alcoholism.