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

Mol Psychiatry. 1999 Nov;4(6):552-7. doi: 10.1038/sj.mp.4000562.

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 (chi2 = 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions / genetics
  • Adult
  • Alcoholism / genetics*
  • Alleles
  • Amino Acid Substitution
  • Brain Chemistry / genetics*
  • Carrier Proteins / genetics*
  • DNA Primers
  • Dopamine Plasma Membrane Transport Proteins
  • Family Health
  • Female
  • Genetic Linkage*
  • Genetic Predisposition to Disease
  • Genotype
  • Haplotypes
  • Humans
  • Japan
  • Male
  • Membrane Glycoproteins*
  • Membrane Transport Proteins*
  • Middle Aged
  • Nerve Tissue Proteins*
  • Polymorphism, Genetic*
  • Schizophrenia / genetics

Substances

  • 3' Untranslated Regions
  • Carrier Proteins
  • DNA Primers
  • Dopamine Plasma Membrane Transport Proteins
  • Membrane Glycoproteins
  • Membrane Transport Proteins
  • Nerve Tissue Proteins
  • SLC6A3 protein, human