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

66 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

Fingerprint

Polymorphism
Neurotransmitter Agents
Genes
Alcoholism
Dopamine D2 Receptors
Genotype
Alcoholics
Reward
varespladib methyl
Dopamine
Ethanol
Amino Acid Transport System X-AG
Gene
Alcoholic Liver Cirrhosis
Serotonin Plasma Membrane Transport Proteins
Dopamine Plasma Membrane Transport Proteins
Alcohol Dehydrogenase
Glutamate Receptors
Enzymes
Metabolism

Keywords

  • Alcoholism
  • Dopamine
  • Genotype
  • Reward

ASJC Scopus subject areas

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

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

Association studies of neurotransmitter gene polymorphisms in alcoholic caucasians. / Foley, P. F.; Loh, E. W.; Innes, D. J.; Williams, S. M.; Tannenberg, A. E.G.; Harper, C. G.; Dodd, P. R.

In: Annals of the New York Academy of Sciences, Vol. 1025, 01.01.2004, p. 39-46.

Research output: Contribution to journalArticle

Foley, P. F. ; Loh, E. W. ; Innes, D. J. ; Williams, S. M. ; Tannenberg, A. E.G. ; Harper, C. G. ; Dodd, P. R. / Association studies of neurotransmitter gene polymorphisms in alcoholic caucasians. In: Annals of the New York Academy of Sciences. 2004 ; Vol. 1025. pp. 39-46.
@article{d3466c32005549e99d6d861f6b4ac290,
title = "Association studies of neurotransmitter gene polymorphisms in alcoholic caucasians",
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.",
keywords = "Alcoholism, Dopamine, Genotype, Reward",
author = "Foley, {P. F.} and Loh, {E. W.} and Innes, {D. J.} and Williams, {S. M.} and Tannenberg, {A. E.G.} and Harper, {C. G.} and Dodd, {P. R.}",
year = "2004",
month = "1",
day = "1",
doi = "10.1196/annals.1316.005",
language = "English",
volume = "1025",
pages = "39--46",
journal = "Annals of the New York Academy of Sciences",
issn = "0077-8923",
publisher = "Blackwell Publishing Ltd",

}

TY - JOUR

T1 - Association studies of neurotransmitter gene polymorphisms in alcoholic caucasians

AU - Foley, P. F.

AU - Loh, E. W.

AU - Innes, D. J.

AU - Williams, S. M.

AU - Tannenberg, A. E.G.

AU - Harper, C. G.

AU - Dodd, P. R.

PY - 2004/1/1

Y1 - 2004/1/1

N2 - 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.

AB - 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.

KW - Alcoholism

KW - Dopamine

KW - Genotype

KW - Reward

UR - http://www.scopus.com/inward/record.url?scp=10444237331&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=10444237331&partnerID=8YFLogxK

U2 - 10.1196/annals.1316.005

DO - 10.1196/annals.1316.005

M3 - Article

VL - 1025

SP - 39

EP - 46

JO - Annals of the New York Academy of Sciences

JF - Annals of the New York Academy of Sciences

SN - 0077-8923

ER -