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Human γ‐aminobutyric acid A receptor α2 gene moderates the acute effects of alcohol and brain mRNA expression
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| Zeitschriftentitel: | Genes, Brain and Behavior |
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| Personen und Körperschaften: | , , , , , |
| In: | Genes, Brain and Behavior, 7, 2008, 4, S. 447-454 |
| Format: | E-Article |
| Sprache: | Englisch |
| veröffentlicht: |
Wiley
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| Schlagwörter: |
| Zusammenfassung: | <jats:p> <jats:bold>γ‐aminobutyric acid A (GABA<jats:sub>A</jats:sub>) 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 GABA<jats:sub>A</jats:sub> receptor (<jats:italic>GABRA2</jats:italic>) and alcoholism. In the present study, we examined the functional relevance of the <jats:italic>GABRA2 </jats:italic>gene in alcohol dependence by assessing brain <jats:italic>GABRA2 </jats:italic>mRNA and GABA<jats:sub>A</jats:sub>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 <jats:italic>GABRA2 </jats:italic>gene moderates sensitivity to the acute effects of alcohol in two independent samples from distinct human alcohol challenge studies. Results indicated that <jats:italic>GABRA2 </jats:italic>mRNA levels significantly differed by <jats:italic>GABRA2 </jats:italic>genotype. <jats:italic>GABRA2 </jats:italic>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 <jats:italic>GABRA2 </jats:italic>× 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 <jats:italic>GABRA2 </jats:italic>gene, sensitivity to the acute effects of alcohol and ultimately alcohol dependence.</jats:bold> </jats:p> |
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| Umfang: | 447-454 |
| ISSN: |
1601-1848
1601-183X |
| DOI: | 10.1111/j.1601-183x.2007.00369.x |