Association Between Alcoholism and γ-Amino Butyric Acid α2 Receptor Subtype in a Russian Population

Authors

  • Jaakko Lappalainen,

    Corresponding author
    1. Department of Psychiatry (JL, LKS, JHK, JG), Yale University School of Medicine, New Haven, Connecticut; VA Connecticut Healthcare System (JL, LKS, JHK, JG), West Haven, Connecticut; St. Petersburg State Pavlov Medical University (EK, MR, SP, AT, EZ), St. Petersburg, Russia; and Department of Psychiatry (JC, HRK), University of Connecticut School of Medicine, Farmington, Connecticut.
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  • Evgeny Krupitsky,

    1. Department of Psychiatry (JL, LKS, JHK, JG), Yale University School of Medicine, New Haven, Connecticut; VA Connecticut Healthcare System (JL, LKS, JHK, JG), West Haven, Connecticut; St. Petersburg State Pavlov Medical University (EK, MR, SP, AT, EZ), St. Petersburg, Russia; and Department of Psychiatry (JC, HRK), University of Connecticut School of Medicine, Farmington, Connecticut.
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  • Mikhail Remizov,

    1. Department of Psychiatry (JL, LKS, JHK, JG), Yale University School of Medicine, New Haven, Connecticut; VA Connecticut Healthcare System (JL, LKS, JHK, JG), West Haven, Connecticut; St. Petersburg State Pavlov Medical University (EK, MR, SP, AT, EZ), St. Petersburg, Russia; and Department of Psychiatry (JC, HRK), University of Connecticut School of Medicine, Farmington, Connecticut.
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  • Sofia Pchelina,

    1. Department of Psychiatry (JL, LKS, JHK, JG), Yale University School of Medicine, New Haven, Connecticut; VA Connecticut Healthcare System (JL, LKS, JHK, JG), West Haven, Connecticut; St. Petersburg State Pavlov Medical University (EK, MR, SP, AT, EZ), St. Petersburg, Russia; and Department of Psychiatry (JC, HRK), University of Connecticut School of Medicine, Farmington, Connecticut.
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  • Anastaisa Taraskina,

    1. Department of Psychiatry (JL, LKS, JHK, JG), Yale University School of Medicine, New Haven, Connecticut; VA Connecticut Healthcare System (JL, LKS, JHK, JG), West Haven, Connecticut; St. Petersburg State Pavlov Medical University (EK, MR, SP, AT, EZ), St. Petersburg, Russia; and Department of Psychiatry (JC, HRK), University of Connecticut School of Medicine, Farmington, Connecticut.
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  • Edwin Zvartau,

    1. Department of Psychiatry (JL, LKS, JHK, JG), Yale University School of Medicine, New Haven, Connecticut; VA Connecticut Healthcare System (JL, LKS, JHK, JG), West Haven, Connecticut; St. Petersburg State Pavlov Medical University (EK, MR, SP, AT, EZ), St. Petersburg, Russia; and Department of Psychiatry (JC, HRK), University of Connecticut School of Medicine, Farmington, Connecticut.
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  • Lucia K. Somberg,

    1. Department of Psychiatry (JL, LKS, JHK, JG), Yale University School of Medicine, New Haven, Connecticut; VA Connecticut Healthcare System (JL, LKS, JHK, JG), West Haven, Connecticut; St. Petersburg State Pavlov Medical University (EK, MR, SP, AT, EZ), St. Petersburg, Russia; and Department of Psychiatry (JC, HRK), University of Connecticut School of Medicine, Farmington, Connecticut.
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  • Jonathan Covault,

    1. Department of Psychiatry (JL, LKS, JHK, JG), Yale University School of Medicine, New Haven, Connecticut; VA Connecticut Healthcare System (JL, LKS, JHK, JG), West Haven, Connecticut; St. Petersburg State Pavlov Medical University (EK, MR, SP, AT, EZ), St. Petersburg, Russia; and Department of Psychiatry (JC, HRK), University of Connecticut School of Medicine, Farmington, Connecticut.
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  • Henry R. Kranzler,

    1. Department of Psychiatry (JL, LKS, JHK, JG), Yale University School of Medicine, New Haven, Connecticut; VA Connecticut Healthcare System (JL, LKS, JHK, JG), West Haven, Connecticut; St. Petersburg State Pavlov Medical University (EK, MR, SP, AT, EZ), St. Petersburg, Russia; and Department of Psychiatry (JC, HRK), University of Connecticut School of Medicine, Farmington, Connecticut.
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  • John H. Krystal,

    1. Department of Psychiatry (JL, LKS, JHK, JG), Yale University School of Medicine, New Haven, Connecticut; VA Connecticut Healthcare System (JL, LKS, JHK, JG), West Haven, Connecticut; St. Petersburg State Pavlov Medical University (EK, MR, SP, AT, EZ), St. Petersburg, Russia; and Department of Psychiatry (JC, HRK), University of Connecticut School of Medicine, Farmington, Connecticut.
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  • Joel Gelernter

    1. Department of Psychiatry (JL, LKS, JHK, JG), Yale University School of Medicine, New Haven, Connecticut; VA Connecticut Healthcare System (JL, LKS, JHK, JG), West Haven, Connecticut; St. Petersburg State Pavlov Medical University (EK, MR, SP, AT, EZ), St. Petersburg, Russia; and Department of Psychiatry (JC, HRK), University of Connecticut School of Medicine, Farmington, Connecticut.
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  • Supported by the National Institutes of Health (K08 AA13732, R01 AA11330, P50 AA12870, M01 RR06192, K05 AA14906, K24 AA13736, and R01 AA011321-04), the Alcoholic Beverage Medical Research Foundation, the US Department of Veterans Affairs (VA Alcohol Research Center, VA Mental Illness Research, Education and Clinical Center, and VA Veterans Research Enhancement Award Program), and the Ethel F. Donaghue Women's Health Investigator Program at Yale.

Reprint requests: Jaakko Lappalainen, MD, PhD, Yale University, VA Connecticut Healthcare System, Psychiatry 116A2, 950 Campbell Avenue, West Haven, CT 06516; Fax: 203-937-3897; E-mail: jaakko.lappalainen@yale.edu.

Abstract

Background:

Two recent large genetic studies in the US population have reported association between genetic variation in γ-amino butyric acid α2 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 χ2 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.

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