More recent reports suggest that the association of the GABRA2 gene with alcoholism may be complicated by moderate linkage disequilibrium of GABRA2 markers with a functional genetic variation in the adjacent GABRG1 gene (Covault et al. 2008; Drgon et al. 2006; Ittiwut et al. 2008). Indeed, Covault et al. (2008) reported that markers in the GABRG1 region on chromosome 4 had the strongest association with ethanol dependence in the European American population. The γ1 subunit-containing GABAA receptors show increased sensitivity to neuroactive steroids compared to the γ2 subunit-containing GABAA receptors (Puia et al. 1993). This subunit is increased in ethanol-dependent rats (Devaud et al. 1995) that are sensitized to the anticonvulsant effects of GABAergic neuroactive steroids (Devaud et al. 1996). Altered sensitivity to neuroactive steroids may affect ethanol sensitivity and therefore modulate risk for ethanol dependence (Morrow et al. 2006). In addition to GABRA2, other genes that encode for the GABAA receptor subunits have been associated with ethanol dependence. Thus, on chromosome 4, association of the GABRB1 gene with alcoholism was reported by several groups (Long et al. 1998; Parsian and Zhang 1999; Reich et al. 1998; Song et al. 2003).
