Role of GABRA2 in Moderating Subjective Responses to Alcohol

Sungwon Roh, Sachio Matsushita, Sachiko Hara, Hitoshi Maesato, Toshifumi Matsui, Go Suzuki, Tomohiro Miyakawa, Vijay A. Ramchandani, Ting Kai Li, Susumu Higuchi

Research output: Contribution to journalArticle

43 Citations (Scopus)

Abstract

Background: Human twin studies have shown that certain responses to alcohol, including subjective perceptions, are genetically influenced. Previous studies have provided evidence that a low level of response to alcohol predicts future alcohol use disorders in humans. Recent genetic studies suggest an association between alcohol dependence and genetic variation in the γ-aminobutyric acid A (GABA A) receptor α2 subunit gene (GABRA2). Based on a haplotypic association of alcohol dependence with GABRA2, we investigated whether GABRA2 alleles are associated with the subjective responses to clamped alcohol concentration. Methods: One hundred and ten healthy social drinkers (53 men) underwent the alcohol clamp. Fifteen minutes after the start of an intravenous infusion of alcohol, the breath alcohol concentration was clamped at a target of 50±5mg/dl for 165minutes. Subjective physiologic responses to alcohol and stimulant and sedative effects of alcohol were measured repeatedly during the alcohol clamp. Because aldehyde dehydrogenase 2 (ALDH2) has been shown to have a great impact on the subjective responses to alcohol, we divided subjects by ALDH2 genotype for further analyses. To examine the role of genetic variation in GABRA2, 7 single nucleotide polymorphisms (SNPs) that were informative in association studies were included as factors in the analysis. Results: Among these 7 SNPs, 3 SNPs (rs279869, rs279858, and rs279837) located in the middle of the GABRA2 gene showed significant associations with subjective effects of alcohol. Subjects with 1 or 2 copies of the more common allele showed greater subjective responses to alcohol than did individuals homozygous for the alcohol dependence-associated allele regardless of ALDH2 genotype. Conclusions: These findings confirm and extend the observation that the GABRA2 alleles affect the subjective responses to alcohol, and suggest that the genetic variations in GABRA2 might play a role in the risk of alcohol use disorders by moderating the subjective effects of alcohol.

Original languageEnglish
Pages (from-to)400-407
Number of pages8
JournalAlcoholism: Clinical and Experimental Research
Volume35
Issue number3
DOIs
StatePublished - 2011 Mar 1

Fingerprint

Alcohols
Aldehyde Dehydrogenase
Alleles
Alcoholism
Single Nucleotide Polymorphism
Polymorphism
Nucleotides
Clamping devices
Genotype
Aminobutyrates
Genes
Twin Studies
Genetic Association Studies
Hypnotics and Sedatives
Intravenous Infusions
Statistical Factor Analysis

Keywords

  • ALDH2
  • Alcohol
  • Alcohol Clamping
  • GABA
  • GABRA2
  • Subjective Response

Cite this

Roh, S., Matsushita, S., Hara, S., Maesato, H., Matsui, T., Suzuki, G., ... Higuchi, S. (2011). Role of GABRA2 in Moderating Subjective Responses to Alcohol. Alcoholism: Clinical and Experimental Research, 35(3), 400-407. https://doi.org/10.1111/j.1530-0277.2010.01357.x
Roh, Sungwon ; Matsushita, Sachio ; Hara, Sachiko ; Maesato, Hitoshi ; Matsui, Toshifumi ; Suzuki, Go ; Miyakawa, Tomohiro ; Ramchandani, Vijay A. ; Li, Ting Kai ; Higuchi, Susumu. / Role of GABRA2 in Moderating Subjective Responses to Alcohol. In: Alcoholism: Clinical and Experimental Research. 2011 ; Vol. 35, No. 3. pp. 400-407.
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Roh, S, Matsushita, S, Hara, S, Maesato, H, Matsui, T, Suzuki, G, Miyakawa, T, Ramchandani, VA, Li, TK & Higuchi, S 2011, 'Role of GABRA2 in Moderating Subjective Responses to Alcohol', Alcoholism: Clinical and Experimental Research, vol. 35, no. 3, pp. 400-407. https://doi.org/10.1111/j.1530-0277.2010.01357.x

Role of GABRA2 in Moderating Subjective Responses to Alcohol. / Roh, Sungwon; Matsushita, Sachio; Hara, Sachiko; Maesato, Hitoshi; Matsui, Toshifumi; Suzuki, Go; Miyakawa, Tomohiro; Ramchandani, Vijay A.; Li, Ting Kai; Higuchi, Susumu.

In: Alcoholism: Clinical and Experimental Research, Vol. 35, No. 3, 01.03.2011, p. 400-407.

Research output: Contribution to journalArticle

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T1 - Role of GABRA2 in Moderating Subjective Responses to Alcohol

AU - Roh, Sungwon

AU - Matsushita, Sachio

AU - Hara, Sachiko

AU - Maesato, Hitoshi

AU - Matsui, Toshifumi

AU - Suzuki, Go

AU - Miyakawa, Tomohiro

AU - Ramchandani, Vijay A.

AU - Li, Ting Kai

AU - Higuchi, Susumu

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