Glutamate decarboxylase genes and alcoholism in Han Taiwanese men.
OBJECTIVE
Glutamate decarboxylase (GAD), the rate-limiting enzyme in the synthesis of gamma-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.


METHODS
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.
Loh
El-Wui
el-W
Division of Mental Health and Drug Abuse Research, National Health Research Institutes, Taipei, Taiwan.
Lane
Hsien-Yuan
HY
Chen
Chien-Hsiun
CH
Chang
Pi-Shan
PS
Ku
Li-Wen
LW
Wang
Kathy H T
KH
Cheng
Andrew T A
AT
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000437:Alcoholism / Q000201:enzymology / Q000235:genetics*; D000483:Alleles; D005787:Gene Frequency; D005838:Genotype; D005968:Glutamate Decarboxylase / Q000235:genetics*; D006239:Haplotypes; D006801:Humans; D007527:Isoenzymes / Q000235:genetics; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012651:Self Medication; D013624:Taiwan / Q000453:epidemiology; D009626:Terminology as Topic; D005680:gamma-Aminobutyric Acid / Q000502:physiology
D007527:Isoenzymes; D005680:gamma-Aminobutyric Acid; D005968:Glutamate Decarboxylase; C402565:glutamate decarboxylase 1; C401141:glutamate decarboxylase 2