Association between alcoholism and gamma-amino butyric acid alpha2 receptor subtype in a Russian population.
BACKGROUND
Two recent large genetic studies in the US population have reported association between genetic variation in gamma-amino butyric acid alpha2 receptor subtype (GABRA2) and risk for alcohol dependence. The goal of this study was to test whether GABRA2 is associated with alcohol dependence in a sample of Russian alcohol-dependent men.


METHODS
A total of 113 Russian alcohol-dependent men and 100 male population control subjects were recruited in St. Petersburg and genotyped for seven GABRA2 single-nucleotide polymorphisms (SNPs) using real-time PCR (TaqMan). Six SNPs were located in a GABRA2 haplotype block previously associated with alcohol dependence (AD) in the US population. SNPs and haplotypes were tested for an association to AD using chi analysis and a likelihood ratio-based statistic implemented in the software COCAPHASE.


RESULTS
Significant associations between two SNPs and AD were observed (p < 0.05). In addition, a trend-level association was observed between AD and three adjacent SNPs (p < 0.1). Associated alleles were carried in a haplotype that was present at frequencies of 0.37 and 0.48 in the control and alcohol-dependent populations, respectively (p < 0.06). Tight linkage disequilibrium spanning from the central portion of the gene to the 3' end was observed in this population. Comparison of the findings to the previously published studies in the US population revealed a highly similar linkage disequilibrium pattern in this population.


CONCLUSIONS
These findings suggest that genetic variants of GABRA2 increase risk for AD in the Russian population and provide additional support to the hypothesis that polymorphic variation at the GABRA2 locus plays an important role in predisposing to AD at least in European-ancestry populations.
Lappalainen
Jaakko
J
Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut 06516, USA. jakko.lappalainen@yale.edu
Krupitsky
Evgeny
E
Remizov
Mikhail
M
Pchelina
Sofia
S
Taraskina
Anastaisa
A
Zvartau
Edwin
E
Somberg
Lucia K
LK
Covault
Jonathan
J
Kranzler
Henry R
HR
Krystal
John H
JH
Gelernter
Joel
J
D000328:Adult; D000437:Alcoholism / Q000453:epidemiology / Q000235:genetics*; D000483:Alleles; D004247:DNA / Q000235:genetics; D005787:Gene Frequency; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D015810:Linkage Disequilibrium / Q000235:genetics; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011963:Receptors, GABA-A / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012307:Risk Factors; D012426:Russia / Q000453:epidemiology
C484841:GABRA2 protein, human; D011963:Receptors, GABA-A; D004247:DNA