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 language | English |
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Pages (from-to) | 1817-1823 |
Number of pages | 7 |
Journal | Alcoholism: Clinical and Experimental Research |
Volume | 30 |
Issue number | 11 |
DOIs | |
Publication status | Published - Nov 2006 |
Externally published | Yes |
Keywords
- Alcohol Dependence
- Anxiety Disorders
- Glutamate Decarboxylase Genes
- γ-Aminobutyric Acid
ASJC Scopus subject areas
- Medicine (miscellaneous)
- Toxicology
- Psychiatry and Mental health