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

Publisher: Nature Publishing Group Specialist Journals Country of Publication: England NLM ID: 9607835 Publication Model: Print Cited Medium: Print ISSN: 1359-4184 (Print) Linking ISSN: 13594184 NLM ISO Abbreviation: Mol Psychiatry Subsets: MEDLINE

Publication: 2000- : Houndmills, Basingstoke, UK : Nature Publishing Group Specialist Journals
Original Publication: Houndmills, Hampshire, UK ; New York, NY : Stockton Press, c1996-

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

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.

0 (3' Untranslated Regions)
0 (Carrier Proteins)
0 (DNA Primers)
0 (Dopamine Plasma Membrane Transport Proteins)
0 (Membrane Glycoproteins)
0 (Membrane Transport Proteins)
0 (Nerve Tissue Proteins)
0 (SLC6A3 protein, human)

Date Created: 19991201 Date Completed: 20000103 Latest Revision: 20191103

20231215

10.1038/sj.mp.4000562

10578237