Glutamate decarboxylase genes and alcoholism in Han Taiwanese men

El Wui Loh, Hsien Yuan Lane, Chien Hsiun Chen, Pi Shan Chang, Li Wen Ku, Kathy H.T. Wang, Andrew T.A. Cheng

Research output: Contribution to journalArticlepeer-review

24 Citations (Scopus)

Abstract

Objective: Glutamate decarboxylase (GAD), the rate-limiting enzyme in the synthesis of γ-aminobutyric acid (GABA), may be involved in the development of alcoholism. This study examined the possible roles of the genes that code for 2 forms of GAD (GAD1 and GAD2) in the development of alcoholism. Method: An association study was conducted among 140 male alcoholic subjects meeting the DSM-III-R criteria for alcohol dependence and 146 controls recruited from the Han Taiwanese in community and clinical settings. Psychiatric assessment of drinking conditions was conducted using a Chinese version of the Schedules for Clinical Assessment in Neuropsychiatry. The SHEsis and Haploview programs were used in statistical analyses. Results: Nine single-nucleotide polymorphisms (SNPs) at the GAD1 gene were valid for further statistics. Between alcoholic subjects and controls, significant differences were found in genotype distributions of SNP1 (p=0.000), SNP2 (p=0.015), SNP4 (p=0.015), SNP5 (p=0.031), SNP6 (p=0.012), and SNP8 (p=0.004) and in allele distributions of SNP1 (p=0.001), SNP2 (p=0.009), and SNP8 (p=0.009). Permutation tests of SNP1, SNP2, and SNP8 demonstrated significant differences in allele frequencies but not in 2 major haplotype blocks. Three valid SNPs at the GAD2 gene demonstrated no associations with alcoholism. Further permutation tests in the only 1 haplotype block or individual SNPs demonstrated no significant differences. Conclusions: This is the first report indicating a possible significant role of the GAD1 gene in the development of alcohol dependence and/or the course of alcohol withdrawal and outcome of alcoholism.

Original languageEnglish
Pages (from-to)1817-1823
Number of pages7
JournalAlcoholism: Clinical and Experimental Research
Volume30
Issue number11
DOIs
Publication statusPublished - Nov 2006
Externally publishedYes

Keywords

  • Alcohol Dependence
  • Anxiety Disorders
  • Glutamate Decarboxylase Genes
  • γ-Aminobutyric Acid

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Toxicology
  • Psychiatry and Mental health

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