Adaptation of Subjective Responses to Alcohol is Affected by an Interaction of GABRA2 Genotype and Recent Drinking. (19th June 2015)

• Record Type: Journal Article
• Authors: 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.
• Is Part Of: Alcoholism. Volume 39:Number 7(2015:Jul.)
• Page Start: 1148
• Page End: 1157
• Publication Date: 2015-06-19
• Subjects: Alcoholism -- Periodicals; Alcoholism -- Periodicals; Alcoolisme; Electronic journals; Périodique électronique (Descripteur de forme); Ressource Internet (Descripteur de forme); 616.861005
• DOI: 10.1111/acer.12749
• Languages: English
• ISSNs: 0145-6008

Abstract

<abstract abstract-type="main" id="acer12749-abs-0001"> <title> <x xml:space="preserve">Abstract</x> </title> <sec id="acer12749-sec-0001" sec-type="section"> <title>Background</title> <p>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<sub>A</sub> receptor genes <italic>GABRG1</italic> and <italic>GABRA2</italic> and recent drinking history on the acute adaptation of subjective responses to alcohol.</p> </sec> <sec id="acer12749-sec-0002" sec-type="section"> <title>Methods</title> <p>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 <italic>GABRA2</italic> and <italic>GABRG1</italic> 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.</p> </sec> <sec id="acer12749-sec-0003" sec-type="section"> <title>Results</title> <p>Recent drinking history (<italic>p</italic> = 0.01), and recent drinking history × genotype interaction (<italic>p</italic> = 0.01) were significantly associated with acute adaptation of the subjective responses to alcohol for the <italic>GABRA2 </italic>SNP rs279858.</p> </sec> <sec id="acer12749-sec-0004" sec-type="section"> <title>Conclusions</title> <p>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 <italic>GABRA2</italic> effect on alcohol dependence may, in part, be due to its effect on subjective responses to alcohol.</p> </sec> </abstract>