Because the genetic variants do not change the protein structure of the GABA-α2 subunit, the associations between these genetic variants and alcoholism are less obvious than those for the alcohol-metabolizing genes. Recent laboratory research has focused on the specific functional aspects of GABRA2 in the etiology of alcoholism. GABRA2 encodes a subtype of one of five subunits that form the commonly occurring GABAA ionotropic receptor. Binding of GABA to this receptor results, among several outcomes, in sedation and relief of anxiety (i.e., anxiolysis). This anxiolytic effect is more closely related to the α2-subunits than to other subunits (e.g., Dixon et al. 2008). Most α2-containing GABA receptors also are key binding sites for benzodiazepines, whereas receptors containing other subunits only show sensitivity to ethanol. The genetic variants in the GABRA2 gene do not result in functional changes in the receptor, and, in fact, little is known about how the variants that are related to the development of alcohol dependence influence GABRA2 activity. Some investigators (Haughey et al. 2008) demonstrated that a variant called rs279858 resulted in changes in the levels of
