A GABRA2 variant is associated with increased stimulation and 'high' following alcohol administration.
- Authors
- Arias, Albert J; Covault, Jonathan; Feinn, Richard; Pond, Timothy; Yang, Bao-Zhu; Ge, Wenjing; Oncken, Cheryl; Kranzler, Henry R
- Year
- 2014
- Journal
- Alcohol and alcoholism (Oxford, Oxfordshire)
- PMID
- 24166645
- DOI
- 10.1093/alcalc/agt163
- PMCID
- PMC3865816
AIMS: Variation in genes encoding GABAA receptor subunits has been implicated in the risk of alcohol dependence (AD). We sought to replicate and extend previous findings of a moderating effect of single nucleotide polymorphisms (SNPs) in GABRA2 (which encodes the GABAA Ξ±-2 subunit) on the subjective effects of alcohol by examining SNPs in this and the adjacent GABRG1 gene on chromosome 4. METHODS: Fifty-two European-Americans (22 males, 28 light drinkers and 24 heavy drinkers) completed 3 laboratory sessions, during which they drank low-dose, high-dose, or placebo alcohol prior to undergoing periodic assessments of stimulation, sedation and drug enjoyment. We genotyped subjects for three SNPs previously associated with AD: rs279858 in GABRA2, and rs7654165 and rs6447493 in GABRG1. RESULTS: Two SNPs were associated with altered stimulatory effects of alcohol as measured on the Biphasic Alcohol Effects Scale, (rs279858: P = 0.0046; rs6447493: P = 0.0023); both effects were in the opposite direction of previous findings. Carriers of the rs279858 C allele experienced greater stimulation from alcohol. Further inspection of the rs6447493 interaction did not support a pharmacogenetic effect. The effects of rs279858 (but not the other two SNPs) on items from a secondary outcome measure, the Drug Effects Questionnaire (DEQ), were significant. Higher ratings by individuals with the C allele were observed on the DEQ items 'feel the alcohol effect' (P < 0.001), 'like the alcohol effect' (P < 0.001) and feel 'high' (P < 0.001). CONCLUSION: We did not find that the GABRG1 SNPs rs7654165 and rs6447493 moderated the effects of alcohol. Greater stimulatory and euphoric effects of alcohol in carriers of the rs279858 C allele may, in part, explain the previously reported association of this allele with AD.
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