Identification of a novel polymorphism of the human dopamine transporter (DAT1) gene and the significant association with alcoholism.
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.
Ueno
S
S
Department of Neuropsychiatry, Ehime University School of Medicine, Shigenobu, Onsen-gun, Ehime 791-0295, Japan. sano@m.ehime-u.ac.jp
Nakamura
M
M
Mikami
M
M
Kondoh
K
K
Ishiguro
H
H
Arinami
T
T
Komiyama
T
T
Mitsushio
H
H
Sano
A
A
Tanabe
H
H
D020413:3' Untranslated Regions / Q000235:genetics; D000328:Adult; D000437:Alcoholism / Q000235:genetics*; D000483:Alleles; D019943:Amino Acid Substitution; D001923:Brain Chemistry / Q000235:genetics*; D002352:Carrier Proteins / Q000235:genetics*; D017931:DNA Primers; D050483:Dopamine Plasma Membrane Transport Proteins; D005192:Family Health; D005260:Female; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D007564:Japan; D008297:Male; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D008875:Middle Aged; D009419:Nerve Tissue Proteins; D011110:Polymorphism, Genetic; D012559:Schizophrenia / Q000235:genetics
D020413:3' Untranslated Regions; D002352:Carrier Proteins; D017931:DNA Primers; D050483:Dopamine Plasma Membrane Transport Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; C493214:SLC6A3 protein, human