Variations in genes encoding the α and γ subunits of the GABAA receptor are associated with risk for alcoholism (Dick et al. 2004; Edenberg et al. 2004); the association of GABRA2 has been replicated in several populations (Covault et al. 2004; Edenberg and Foroud 2006; Enoch et al. 2006; Fehr et al. 2006; Lappalainen et al. 2005; Soyka et al. 2008). Variations in GABRA2 have also been associated with power in the beta frequency band (13–28 Hz) of the EEG (Edenberg et al. 2004). Yet the associated variations did not affect the amino acid sequences, suggesting that expression differences might be involved (Edenberg et al. 2004). Alternative splicing and alternative promoter use have been demonstrated in the human GABRA2 gene (Tian et al. 2005). To test the hypothesis that variations in the ratios of GABAA receptor subunits would affect receptor function, we manipulated the subunit ratios in the Xenopus oocyte expression system and measured the resulting GABA currents. We modeled changes in gene expression by injecting Xenopus oocytes with different ratios of α2, β2 and γ3 subunits and then compared GABA currents.
