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Adaptation of Subjective Responses to Alcohol is Affected by an Interaction of GABRA2 Genotype and Recent Drinking
Author(s) -
Kosobud Ann E. K.,
Wetherill Leah,
Plawecki Martin H.,
Kareken David A.,
Liang Tiebing,
Nurnberger John L.,
Windisch Kyle,
Xuei Xiaoling,
Edenberg Howard J.,
Foroud Tatiana M.,
O'Connor Sean J.
Publication year - 2015
Publication title -
alcoholism: clinical and experimental research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.267
H-Index - 153
eISSN - 1530-0277
pISSN - 0145-6008
DOI - 10.1111/acer.12749
Subject(s) - psychology , anxiety , alcohol , placebo , alcohol abuse , alcohol intoxication , alcohol dependence , medicine , poison control , psychiatry , injury prevention , chemistry , environmental health , pathology , biochemistry , alternative medicine
Background Subjective perceptions of alcohol intoxication are associated with altered risk for alcohol abuse and dependence. Acute adaptation of these perceptions may influence such risk and may involve genes associated with pleasant perceptions or the relief of anxiety. This study assessed the effect of variation in the GABA A receptor genes GABRG 1 and GABRA 2 and recent drinking history on the acute adaptation of subjective responses to alcohol. Methods One hundred and thirty‐two nondependent moderate to heavy drinkers, aged 21 to 27, participated in 2 single‐blind, counterbalanced sessions, approximately 1 week apart. One session was an intravenous alcohol “clamp,” during which breath alcohol concentration was held steady at 60 mg/dl (60 mg%) for 3 hours, and the other an identical session using saline infusion. Subjective perceptions of Intoxication, Enjoyment, Stimulation, Relaxation, Anxiety, Tiredness, and Estimated Number of Drinks were acquired before (baseline), and during the first and final 45 minutes of the clamp. A placebo‐adjusted index of the subject's acute adaptation to alcohol was calculated for each of the 7 subjective measures and used in a principal component analysis to create a single aggregate estimate for each subject's adaptive response to alcohol. Analysis of covariance tested whether GABRA 2 and GABRG 1 single nucleotide polymorphism ( SNP ) genotypes, gender, placebo session, family history of alcoholism, recent drinking history, and the genotype × recent drinking history interaction significantly predicted the adaptive response. Results Recent drinking history ( p = 0.01), and recent drinking history × genotype interaction ( p = 0.01) were significantly associated with acute adaptation of the subjective responses to alcohol for the GABRA 2 SNP rs279858. Conclusions Higher recent drinking was found to be associated with reduced acute tolerance to positive, stimulating effects of alcohol in carriers of the rs279858 risk allele. We postulate that the GABRA 2 effect on alcohol dependence may, in part, be due to its effect on subjective responses to alcohol.