A Polymorphism in GABRA2 Is Associated With the Medial Frontal Response to Alcohol Cues in an fMRI Study
Article first published online: 4 AUG 2010
Copyright © 2010 by the Research Society on Alcoholism
Alcoholism: Clinical and Experimental Research
Volume 34, Issue 12, pages 2169–2178, December 2010
How to Cite
Kareken, D. A., Liang, T., Wetherill, L., Dzemidzic, M., Bragulat, V., Cox, C., Talavage, T., O’Connor, S. J. and Foroud, T. (2010), A Polymorphism in GABRA2 Is Associated With the Medial Frontal Response to Alcohol Cues in an fMRI Study. Alcoholism: Clinical and Experimental Research, 34: 2169–2178. doi: 10.1111/j.1530-0277.2010.01293.x
- Issue published online: 18 NOV 2010
- Article first published online: 4 AUG 2010
- Received for publication March 26, 2010; accepted June 18, 2010.
Background: Significant evidence has accumulated to suggest an association between single-nucleotide polymorphisms (SNPs) in the GABRA2 gene and alcoholism. However, research has yet to show an association between these polymorphisms and the human brain’s reward system function. In this study, we stratified subjects who had participated in an fMRI study of alcohol cue responses according to their genotype at a SNP in GABRA2 (rs279871) shown to be associated with alcohol dependence (Edenberg et al., 2004).
Methods: Genotyping showed 13 subjects to be homozygous for the high-risk allele (AA), and 23 subjects to be heterozygous (AG). In fMRI, subjects were exposed to the aromas of their preferred alcoholic drink odors (AO), as well as to appetitive control odors (ApCO) under both alcohol intoxication and placebo control conditions.
Results: Homozygous AA subjects had a larger [AO > ApCO] response than did AG subjects in medial frontal cortical areas thought to code reward value. However, AG subjects had a larger [AO > ApCO] effect in the ventral tegmental area. Alcohol intoxication did not alter these group differences.
Conclusions: These are the first data to suggest that GABRA2 genotype could affect the brain’s responses to cues associated with alcohol.