Despite this evidence, the precise function of GABRA2 in general, and more specifically, variants studied in humans, remains elusive. The AA genotype of rs279858 is associated with greater GABRA2 mRNA expression in the prefrontal cortex; however, these mRNA levels did not differ across postmortem brains from alcohol dependent and non-dependent donors [30]. Further, studies imply that the association signal for GABRA2 may actually arise from the neighboring GABRG1 gene [31, 32]. Both GABRA2 and GABRG1 expression appear to be down-regulated in the hippocampus of alcohol dependent individuals [33]. As γ1-subunit containing GABAA receptors are only expressed in selected brain regions (e.g., central amygdala) that have been implicated in addiction, they have emerged as possible therapeutic targets [34]. However, the extent to which these receptors respond to ethanol remains unknown.
