Role of GABRA2 in Moderating Subjective Responses to Alcohol
2010; Wiley; Volume: 35; Issue: 3 Linguagem: Inglês
10.1111/j.1530-0277.2010.01357.x
ISSN1530-0277
AutoresSungwon Roh, Sachio Matsushita, Sachiko Hara, Hitoshi Maesato, Toshifumi Matsui, Go Suzuki, Tomohiro Miyakawa, Vijay A. Ramchandani, Ting‐Kai Li, Higuchi Susumu,
Tópico(s)Neurotransmitter Receptor Influence on Behavior
ResumoAlcoholism: Clinical and Experimental ResearchVolume 35, Issue 3 p. 400-407 Role of GABRA2 in Moderating Subjective Responses to Alcohol Sungwon Roh, Sungwon Roh From the Division of Clinical Research (SR, S Hara), Department of Psychiatry (SM, HM, GS, T Miyakawa, S Higuchi), and Department of Internal Medicine (T Matsui), National Hospital Organization Kurihama Alcoholism Center, Yokosuka, Kanagawa, Japan; Laboratory of Clinical and Translational Studies (VAR) and Office of the Director (TKL), National Institute on Alcohol Abuse and Alcoholism, Bethesda, Maryland.Search for more papers by this authorSachio Matsushita, Sachio Matsushita From the Division of Clinical Research (SR, S Hara), Department of Psychiatry (SM, HM, GS, T Miyakawa, S Higuchi), and Department of Internal Medicine (T Matsui), National Hospital Organization Kurihama Alcoholism Center, Yokosuka, Kanagawa, Japan; Laboratory of Clinical and Translational Studies (VAR) and Office of the Director (TKL), National Institute on Alcohol Abuse and Alcoholism, Bethesda, Maryland.Search for more papers by this authorSachiko Hara, Sachiko Hara From the Division of Clinical Research (SR, S Hara), Department of Psychiatry (SM, HM, GS, T Miyakawa, S Higuchi), and Department of Internal Medicine (T Matsui), National Hospital Organization Kurihama Alcoholism Center, Yokosuka, Kanagawa, Japan; Laboratory of Clinical and Translational Studies (VAR) and Office of the Director (TKL), National Institute on Alcohol Abuse and Alcoholism, Bethesda, Maryland.Search for more papers by this authorHitoshi Maesato, Hitoshi Maesato From the Division of Clinical Research (SR, S Hara), Department of Psychiatry (SM, HM, GS, T Miyakawa, S Higuchi), and Department of Internal Medicine (T Matsui), National Hospital Organization Kurihama Alcoholism Center, Yokosuka, Kanagawa, Japan; Laboratory of Clinical and Translational Studies (VAR) and Office of the Director (TKL), National Institute on Alcohol Abuse and Alcoholism, Bethesda, Maryland.Search for more papers by this authorToshifumi Matsui, Toshifumi Matsui From the Division of Clinical Research (SR, S Hara), Department of Psychiatry (SM, HM, GS, T Miyakawa, S Higuchi), and Department of Internal Medicine (T Matsui), National Hospital Organization Kurihama Alcoholism Center, Yokosuka, Kanagawa, Japan; Laboratory of Clinical and Translational Studies (VAR) and Office of the Director (TKL), National Institute on Alcohol Abuse and Alcoholism, Bethesda, Maryland.Search for more papers by this authorGo Suzuki, Go Suzuki From the Division of Clinical Research (SR, S Hara), Department of Psychiatry (SM, HM, GS, T Miyakawa, S Higuchi), and Department of Internal Medicine (T Matsui), National Hospital Organization Kurihama Alcoholism Center, Yokosuka, Kanagawa, Japan; Laboratory of Clinical and Translational Studies (VAR) and Office of the Director (TKL), National Institute on Alcohol Abuse and Alcoholism, Bethesda, Maryland.Search for more papers by this authorTomohiro Miyakawa, Tomohiro Miyakawa From the Division of Clinical Research (SR, S Hara), Department of Psychiatry (SM, HM, GS, T Miyakawa, S Higuchi), and Department of Internal Medicine (T Matsui), National Hospital Organization Kurihama Alcoholism Center, Yokosuka, Kanagawa, Japan; Laboratory of Clinical and Translational Studies (VAR) and Office of the Director (TKL), National Institute on Alcohol Abuse and Alcoholism, Bethesda, Maryland.Search for more papers by this authorVijay A. Ramchandani, Vijay A. Ramchandani From the Division of Clinical Research (SR, S Hara), Department of Psychiatry (SM, HM, GS, T Miyakawa, S Higuchi), and Department of Internal Medicine (T Matsui), National Hospital Organization Kurihama Alcoholism Center, Yokosuka, Kanagawa, Japan; Laboratory of Clinical and Translational Studies (VAR) and Office of the Director (TKL), National Institute on Alcohol Abuse and Alcoholism, Bethesda, Maryland.Search for more papers by this authorTing-Kai Li, Ting-Kai Li From the Division of Clinical Research (SR, S Hara), Department of Psychiatry (SM, HM, GS, T Miyakawa, S Higuchi), and Department of Internal Medicine (T Matsui), National Hospital Organization Kurihama Alcoholism Center, Yokosuka, Kanagawa, Japan; Laboratory of Clinical and Translational Studies (VAR) and Office of the Director (TKL), National Institute on Alcohol Abuse and Alcoholism, Bethesda, Maryland.Search for more papers by this authorSusumu Higuchi, Susumu Higuchi From the Division of Clinical Research (SR, S Hara), Department of Psychiatry (SM, HM, GS, T Miyakawa, S Higuchi), and Department of Internal Medicine (T Matsui), National Hospital Organization Kurihama Alcoholism Center, Yokosuka, Kanagawa, Japan; Laboratory of Clinical and Translational Studies (VAR) and Office of the Director (TKL), National Institute on Alcohol Abuse and Alcoholism, Bethesda, Maryland.Search for more papers by this author Sungwon Roh, Sungwon Roh From the Division of Clinical Research (SR, S Hara), Department of Psychiatry (SM, HM, GS, T Miyakawa, S Higuchi), and Department of Internal Medicine (T Matsui), National Hospital Organization Kurihama Alcoholism Center, Yokosuka, Kanagawa, Japan; Laboratory of Clinical and Translational Studies (VAR) and Office of the Director (TKL), National Institute on Alcohol Abuse and Alcoholism, Bethesda, Maryland.Search for more papers by this authorSachio Matsushita, Sachio Matsushita From the Division of Clinical Research (SR, S Hara), Department of Psychiatry (SM, HM, GS, T Miyakawa, S Higuchi), and Department of Internal Medicine (T Matsui), National Hospital Organization Kurihama Alcoholism Center, Yokosuka, Kanagawa, Japan; Laboratory of Clinical and Translational Studies (VAR) and Office of the Director (TKL), National Institute on Alcohol Abuse and Alcoholism, Bethesda, Maryland.Search for more papers by this authorSachiko Hara, Sachiko Hara From the Division of Clinical Research (SR, S Hara), Department of Psychiatry (SM, HM, GS, T Miyakawa, S Higuchi), and Department of Internal Medicine (T Matsui), National Hospital Organization Kurihama Alcoholism Center, Yokosuka, Kanagawa, Japan; Laboratory of Clinical and Translational Studies (VAR) and Office of the Director (TKL), National Institute on Alcohol Abuse and Alcoholism, Bethesda, Maryland.Search for more papers by this authorHitoshi Maesato, Hitoshi Maesato From the Division of Clinical Research (SR, S Hara), Department of Psychiatry (SM, HM, GS, T Miyakawa, S Higuchi), and Department of Internal Medicine (T Matsui), National Hospital Organization Kurihama Alcoholism Center, Yokosuka, Kanagawa, Japan; Laboratory of Clinical and Translational Studies (VAR) and Office of the Director (TKL), National Institute on Alcohol Abuse and Alcoholism, Bethesda, Maryland.Search for more papers by this authorToshifumi Matsui, Toshifumi Matsui From the Division of Clinical Research (SR, S Hara), Department of Psychiatry (SM, HM, GS, T Miyakawa, S Higuchi), and Department of Internal Medicine (T Matsui), National Hospital Organization Kurihama Alcoholism Center, Yokosuka, Kanagawa, Japan; Laboratory of Clinical and Translational Studies (VAR) and Office of the Director (TKL), National Institute on Alcohol Abuse and Alcoholism, Bethesda, Maryland.Search for more papers by this authorGo Suzuki, Go Suzuki From the Division of Clinical Research (SR, S Hara), Department of Psychiatry (SM, HM, GS, T Miyakawa, S Higuchi), and Department of Internal Medicine (T Matsui), National Hospital Organization Kurihama Alcoholism Center, Yokosuka, Kanagawa, Japan; Laboratory of Clinical and Translational Studies (VAR) and Office of the Director (TKL), National Institute on Alcohol Abuse and Alcoholism, Bethesda, Maryland.Search for more papers by this authorTomohiro Miyakawa, Tomohiro Miyakawa From the Division of Clinical Research (SR, S Hara), Department of Psychiatry (SM, HM, GS, T Miyakawa, S Higuchi), and Department of Internal Medicine (T Matsui), National Hospital Organization Kurihama Alcoholism Center, Yokosuka, Kanagawa, Japan; Laboratory of Clinical and Translational Studies (VAR) and Office of the Director (TKL), National Institute on Alcohol Abuse and Alcoholism, Bethesda, Maryland.Search for more papers by this authorVijay A. Ramchandani, Vijay A. Ramchandani From the Division of Clinical Research (SR, S Hara), Department of Psychiatry (SM, HM, GS, T Miyakawa, S Higuchi), and Department of Internal Medicine (T Matsui), National Hospital Organization Kurihama Alcoholism Center, Yokosuka, Kanagawa, Japan; Laboratory of Clinical and Translational Studies (VAR) and Office of the Director (TKL), National Institute on Alcohol Abuse and Alcoholism, Bethesda, Maryland.Search for more papers by this authorTing-Kai Li, Ting-Kai Li From the Division of Clinical Research (SR, S Hara), Department of Psychiatry (SM, HM, GS, T Miyakawa, S Higuchi), and Department of Internal Medicine (T Matsui), National Hospital Organization Kurihama Alcoholism Center, Yokosuka, Kanagawa, Japan; Laboratory of Clinical and Translational Studies (VAR) and Office of the Director (TKL), National Institute on Alcohol Abuse and Alcoholism, Bethesda, Maryland.Search for more papers by this authorSusumu Higuchi, Susumu Higuchi From the Division of Clinical Research (SR, S Hara), Department of Psychiatry (SM, HM, GS, T Miyakawa, S Higuchi), and Department of Internal Medicine (T Matsui), National Hospital Organization Kurihama Alcoholism Center, Yokosuka, Kanagawa, Japan; Laboratory of Clinical and Translational Studies (VAR) and Office of the Director (TKL), National Institute on Alcohol Abuse and Alcoholism, Bethesda, Maryland.Search for more papers by this author First published: 30 November 2010 https://doi.org/10.1111/j.1530-0277.2010.01357.xCitations: 45 Reprint requests: Susumu Higuchi, MD, PhD, Department of Psychiatry, National Hospital Organization Kurihama Alcoholism Center, 5-3-1 Nobi, Yokosuka, Kanagawa 239-0841, Japan; Fax: +81-46-849-7743; E-mail: h-susumu@db3.so-net.ne.jp Present address: Department of Mental Health Research, Seoul National Hospital (SR), Seoul, Korea; Department of Psychiatry, National Defense Medical College (GS), Saitama, Japan; Department of Psychiatry and Behavioral Sciences, Duke University School of Medicine (TKL), Durham, North Carolina. Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat 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 (GABAA) 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 ± 5 mg/dl for 165 minutes. 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. Citing Literature Volume35, Issue3March 2011Pages 400-407 RelatedInformation
Referência(s)