This author was an Outstanding Young Investigator Awardee, 8th Annual Meeting of the International Behavioural and Neural Genetics Society, Vancouver, BC, Canada, May 19–22, 2006.
Human γ-aminobutyric acid A receptor α2 gene moderates the acute effects of alcohol and brain mRNA expression
Article first published online: 19 DEC 2007
© 2007 The Authors Journal compilation © 2007 Blackwell Publishing Ltd
Genes, Brain and Behavior
Volume 7, Issue 4, pages 447–454, June 2008
How to Cite
Haughey, H. M., Ray, L. A., Finan, P., Villanueva, R., Niculescu, M. and Hutchison, K. E. (2008), Human γ-aminobutyric acid A receptor α2 gene moderates the acute effects of alcohol and brain mRNA expression. Genes, Brain and Behavior, 7: 447–454. doi: 10.1111/j.1601-183X.2007.00369.x
- Issue published online: 19 DEC 2007
- Article first published online: 19 DEC 2007
- Received 2 May 2007, revised 24 October 2007, accepted for publication 28 October 2007
γ-aminobutyric acid A (GABAA) receptors moderate several of the behavioral effects of alcohol. In fact, recent studies have shown an association between the gene for the α2-subunit of the GABAA receptor (GABRA2) and alcoholism. In the present study, we examined the functional relevance of the GABRA2 gene in alcohol dependence by assessing brain GABRA2 mRNA and GABAAα2-subunit protein levels in post-mortem prefrontal cortical tissue collected from control and alcohol-dependent individuals. In addition, using an endophenotype approach, we tested whether the GABRA2 gene moderates sensitivity to the acute effects of alcohol in two independent samples from distinct human alcohol challenge studies. Results indicated that GABRA2 mRNA levels significantly differed by GABRA2 genotype. GABRA2 single nucleotide polymorphisms (rs573400, rs279871 and rs279858) were significantly associated with sensitivity to the acute effects of alcohol. Specifically, there was a significant main effect of GABRA2 × breath alcohol concentration on several measures of subjective responses to alcohol, including the hedonic value of alcohol. Importantly, reanalysis of a previous intravenous alcohol administration study confirmed the results of the oral alcohol challenge study. In summary, these results extend previous findings and provide new insights into the putative biobehavioral mechanisms that may moderate the association between the GABRA2 gene, sensitivity to the acute effects of alcohol and ultimately alcohol dependence.