Association studies of neurotransmitter gene polymorphisms in alcoholic caucasians

P. F. Foley, E. W. Loh, D. J. Innes, S. M. Williams, A. E.G. Tannenberg, C. G. Harper, P. R. Dodd

Research output: Contribution to journalArticle

69 Citations (Scopus)

Abstract

Ethanol enhances mesolimbic/cortical dopamine activity in reward and reinforcement circuits. We investigated the hypothesis that risk for alcoholism may be mediated by genes for neurotransmitters associated with the dopamine reward system as well as genes for enzymes involved in ethanol metabolism. DNA was extracted from brain tissue collected at autopsy from pathologically characterized alcoholics and controls. PCR-based assays showed that alcoholism was associated with polymorphisms of the dopamine D2 receptor (DRD2) TaqI B (P = .029) and the GABAA-β2 subunit C1412T (P = .012) genes, but not with the glutamate receptor subunit gene NMDAR2B (366C/G), the serotonin transporter gene (5HTTL-PR), the dopamine transporter gene DAT1(SLC6A3), the dopamine D2 receptor gene DRD2 TaqI A, or the GABAA α1(A15G), α6(T1519C), and γ2(G3145A) subunit genes. The glial glutamate transporter gene EAAT2 polymorphism G603A was associated with alcoholic cirrhosis (P = .048). The genotype for the most active alcohol dehydrogenase enzyme ADH1C was associated with a lower risk of alcoholism (P = .026) and was less prevalent in alcoholics with DRD2TaqIA2/A2 (P = .047), GABA A-β2 1412C/C (P = .01), or EAAT2 603G/A (P = .022) genotypes. Combined DRD2TaqI A or B with GABAA-β2 or EAAT2 G603A genotypes may have a concerted influence in the predisposition to alcoholism.

Original languageEnglish
Pages (from-to)39-46
Number of pages8
JournalAnnals of the New York Academy of Sciences
Volume1025
DOIs
Publication statusPublished - Jan 1 2004
Externally publishedYes

Keywords

  • Alcoholism
  • Dopamine
  • Genotype
  • Reward

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • History and Philosophy of Science

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  • Cite this

    Foley, P. F., Loh, E. W., Innes, D. J., Williams, S. M., Tannenberg, A. E. G., Harper, C. G., & Dodd, P. R. (2004). Association studies of neurotransmitter gene polymorphisms in alcoholic caucasians. Annals of the New York Academy of Sciences, 1025, 39-46. https://doi.org/10.1196/annals.1316.005