Alcohol-Induced Stimulation Mediates the Effect of a GABRA2 SNP on Alcohol Self-Administrated among Alcohol-Dependent Individuals.
BACKGROUND
A single-nucleotide polymorphism (SNP) in GABRA2 (rs279858) may moderate subjective response (SR) to alcohol. Results of studies in non-dependent drinkers examining this GABRA2 SNP on SR have been equivocal. This study examined this SNP's direct and indirect effects on alcohol self-administration in dependent drinkers.


METHODS
The sample consisted of 63 Caucasian, non-treatment-seeking individuals with alcohol dependence. Subjective stimulation was assessed using the Biphasic Alcohol Effects Scale following consumption of an alcoholic priming drink (target breath alcohol content = 0.02 g%). Participants were subsequently offered the opportunity to self-administer up to eight additional drinks.


RESULTS
Controlling for baseline stimulation, T-allele homozygotes, relative to individuals with at least one copy of the C-allele, reported greater initial stimulation, t(58) = 2.011, p = 0.049. Greater stimulation predicted greater subsequent alcohol self-administration, t(57) = 2.522, p = 0.015. Although rs279858 genotype did not directly impact self-administration (t(57) = -0.674, p = 0.503), it did have an indirect effect (95% confidence interval [0.068, 1.576]), such that T-allele homozygotes reported greater stimulation, which in turn predicted greater self-administration.


CONCLUSIONS
These results suggest that the influence of this SNP on SR differs depending on dose or stage of dependence. This study is the first to demonstrate an indirect effect of rs279858 genotype on drinking through SR. Although C-allele carriers have been shown to have an increased risk for alcohol dependence, in our dependent sample, greater stimulation was found among T-allele homozygotes, suggesting that the influence of SR on developing and maintaining dependence differs based on rs279858 genotype.This study demonstrates an indirect effect of rs279858 genotype on drinking through SR. Although C-allele carriers have an increased risk for alcohol dependence, in our dependent sample, greater stimulation was found among T-allele homozygotes, suggesting that the influence of SR on developing dependence differs based on rs279858 genotype.
Charleston Alcohol Research Center, Department of Psychiatry and Behavioral Sciences, Medical University of South Carolina, Charleston, SC, USA.
Stephen J
SJ
Boyd
Charleston Alcohol Research Center, Department of Psychiatry and Behavioral Sciences, Medical University of South Carolina, Charleston, SC, USA.
Joseph P
JP
Schacht
Charleston Alcohol Research Center, Department of Psychiatry and Behavioral Sciences, Medical University of South Carolina, Charleston, SC, USA.
James J
JJ
Prisciandaro
Charleston Alcohol Research Center, Department of Psychiatry and Behavioral Sciences, Medical University of South Carolina, Charleston, SC, USA.
Konstantin
K
Voronin
Charleston Alcohol Research Center, Department of Psychiatry and Behavioral Sciences, Medical University of South Carolina, Charleston, SC, USA antonr@musc.edu.
Raymond F
RF
Anton
D000328:Adult; D000428:Alcohol Drinking / Q000235:genetics / Q000503:physiopathology; D000437:Alcoholism / Q000235:genetics* / Q000503:physiopathology; D000483:Alleles; D000431:Ethanol / Q000494:pharmacology*; D005260:Female; D006720:Homozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011963:Receptors, GABA-A / Q000235:genetics* / Q000502:physiology; D055815:Young Adult
C484841:GABRA2 protein, human; D011963:Receptors, GABA-A; D000431:Ethanol