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Saturday, November 17, 2007

The human GABAA receptor α2 gene moderates the acute effects of alcohol and brain mRNA expression
Genes, Brain and Behavior (OnlineAccepted Articles). 13 November 2007



γ-Aminobutyric acid A (GABAA) receptors moderate several of the behavioral effects of alcohol. In fact, recent studies have demonstrated 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 GABAA α2 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, rs279858) were significantly associated with sensitivity to the acute effects of alcohol. Specifically, there was a significant main effect of GABRA2 x Breath Alcohol Concentration (BrAC) on several measures of subjective responses to alcohol, including the hedonic value of alcohol. Importantly, re-analysis 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 insight 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.

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