Association between variants at the GABAAβ2, GABAAα6 and GABAAγ2 gene cluster and alcohol dependence in a Scottish population

A Corrigendum to this article was published on 30 June 2000

Abstract

A role for the GABA/benzodiazepine receptor complex in alcohol dependence syndrome has been suggested by several lines of evidence. To elucidate the role of GABAA subunits in human alcohol dependence syndrome, we identified polymorphisms in the GABAAβ2 and GABAAα6 receptor subunit genes on 5q33 and assessed their potential contribution in an association study, together with a NciI RFLP at the GABAAγ2 receptor subunit gene. One hundred and eight alcohol-dependent subjects and 54 unrelated controls were recruited from Scotland. Two novel genetic markers were identified at the GABAAβ2 and GABAAα6 receptor subunit genes and examined for association with the alcohol dependence syndrome and subgroups of subjects with Korsakoff's psychosis and without Korsakoff's psychosis, together with a NciI RFLP at the GABAAγ2 receptor subunit gene. The χ2 tests demonstrated associations between all alcohol-dependent subjects (not stratified) and the BanI RFLP at the GABAAβ2 receptor subunit gene (P = 0.015), and the AlwNI RFLP at the GABAAα6 receptor gene (P = 0.013). Significant associations were also found between the alcohol-dependent subjects with Korsakoff's psychosis and the BanI RFLP (P = 0.039) and the AlwNI RFLP (P = 0.003). Haplotype analysis also provided evidence of association when all alcohol-dependent subjects (P = 0.013) and the subjects with Korsakoff's psychosis (P = 0.007) were compared with controls. Our findings provide evidence for a role for the GABAA receptor subunit cluster on chromosome 5q33 in susceptibility to the alcohol dependence syndrome and Korsakoff's psychosis.

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Correspondence to D Ball.

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Loh, EW., Smith, I., Murray, R. et al. Association between variants at the GABAAβ2, GABAAα6 and GABAAγ2 gene cluster and alcohol dependence in a Scottish population. Mol Psychiatry 4, 539–544 (1999). https://doi.org/10.1038/sj.mp.4000554

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Keywords

  • alcohol dependence
  • Korsakoff's psychosis
  • chromosome 5
  • GABAA subunit receptor genes
  • genetic polymorphisms

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