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Adaptation of Subjective Responses to Alcohol is Affected by an Interaction of GABRA2 Genotype and Recent Drinking.
Alcohol Clin Exp Res. 2015 Jul; 39(7):1148-57.AC

Abstract

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 GABAA receptor genes GABRG1 and GABRA2 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 GABRA2 and GABRG1 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 GABRA2 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 GABRA2 effect on alcohol dependence may, in part, be due to its effect on subjective responses to alcohol.

Authors+Show Affiliations

Department of Neurology, Indiana University School of Medicine, Indianapolis, Indiana.Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, Indiana. Department of Psychology, Indiana University Purdue University at Indianapolis, Indianapolis, Indiana.Department of Psychiatry, Indiana University School of Medicine, Indianapolis, Indiana.Department of Neurology, Indiana University School of Medicine, Indianapolis, Indiana.Department of Medicine, Division of Endocrinology, Indiana University School of Medicine, Indianapolis, Indiana.Department of Psychiatry, Indiana University School of Medicine, Indianapolis, Indiana.Department of Psychology, Indiana University Purdue University at Indianapolis, Indianapolis, Indiana.Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, Indiana.Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, Indiana. Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, Indiana.Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, Indiana.Department of Psychiatry, Indiana University School of Medicine, Indianapolis, Indiana. R.L. Roudebush Veterans Administration Medical Center, Indianapolis, Indiana.

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

26087834

Citation

Kosobud, Ann E K., et al. "Adaptation of Subjective Responses to Alcohol Is Affected By an Interaction of GABRA2 Genotype and Recent Drinking." Alcoholism, Clinical and Experimental Research, vol. 39, no. 7, 2015, pp. 1148-57.
Kosobud AE, Wetherill L, Plawecki MH, et al. Adaptation of Subjective Responses to Alcohol is Affected by an Interaction of GABRA2 Genotype and Recent Drinking. Alcohol Clin Exp Res. 2015;39(7):1148-57.
Kosobud, A. E., Wetherill, L., Plawecki, M. H., Kareken, D. A., Liang, T., Nurnberger, J. L., Windisch, K., Xuei, X., Edenberg, H. J., Foroud, T. M., & O'Connor, S. J. (2015). Adaptation of Subjective Responses to Alcohol is Affected by an Interaction of GABRA2 Genotype and Recent Drinking. Alcoholism, Clinical and Experimental Research, 39(7), 1148-57. https://doi.org/10.1111/acer.12749
Kosobud AE, et al. Adaptation of Subjective Responses to Alcohol Is Affected By an Interaction of GABRA2 Genotype and Recent Drinking. Alcohol Clin Exp Res. 2015;39(7):1148-57. PubMed PMID: 26087834.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Adaptation of Subjective Responses to Alcohol is Affected by an Interaction of GABRA2 Genotype and Recent Drinking. AU - Kosobud,Ann E K, AU - Wetherill,Leah, AU - Plawecki,Martin H, AU - Kareken,David A, AU - Liang,Tiebing, AU - Nurnberger,John L, AU - Windisch,Kyle, AU - Xuei,Xiaoling, AU - Edenberg,Howard J, AU - Foroud,Tatiana M, AU - O'Connor,Sean J, Y1 - 2015/06/19/ PY - 2014/03/03/received PY - 2015/03/30/accepted PY - 2015/6/20/entrez PY - 2015/6/20/pubmed PY - 2016/4/12/medline KW - Acute Tolerance KW - Alcohol Use Disorders KW - Family History of Alcoholism KW - GABA Receptors KW - Intravenous Alcohol SP - 1148 EP - 57 JF - Alcoholism, clinical and experimental research JO - Alcohol Clin Exp Res VL - 39 IS - 7 N2 - 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 GABAA receptor genes GABRG1 and GABRA2 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 GABRA2 and GABRG1 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 GABRA2 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 GABRA2 effect on alcohol dependence may, in part, be due to its effect on subjective responses to alcohol. SN - 1530-0277 UR - https://www.unboundmedicine.com/medline/citation/26087834/Adaptation_of_Subjective_Responses_to_Alcohol_is_Affected_by_an_Interaction_of_GABRA2_Genotype_and_Recent_Drinking_ L2 - https://doi.org/10.1111/acer.12749 DB - PRIME DP - Unbound Medicine ER -