Our data show that for all 7 subjective measures, acute tolerance to alcohol developed within 3 hours when BrAC was held at 60 mg/dL. The placebo-adjusted adaptive responses calculated for each of the 7 measures were combined into a single index, PC1, using principal components analysis. PC1 was tested for the effects of SNPs in GABRA2 and GABRG1. The model that included rs279858 (in GABRA2) found recent drinking history was associated with acute tolerance (p=0.01). Although that SNP itself showed only a trend toward significance, there was a significant recent drinking history x genotype interaction (p=0.01). Among individuals who reported higher levels of drinking in the preceding 30 days, those carrying the T allele showed more tolerance than high-drinking individuals with the CC genotype. Conversely, among individuals who reported lower drinking in the preceding 30 days, those carrying the T allele showed less tolerance than those with the CC genotype (Figure 4). The C allele of this SNP has been associated with alcohol dependence (Fehr et al., 2008, Covault et al., 2008). The model that included rs1497577 (in GABRG1) demonstrated no such association.
