Involvement of the atrial natriuretic peptide transcription factor GATA4 in alcohol dependence, relapse risk and treatment response to acamprosate

被引：0
作者：
F Kiefer
S H Witt
J Frank
A Richter
J Treutlein
T Lemenager
M M Nöthen
S Cichon
A Batra
M Berner
N Wodarz
U S Zimmermann
R Spanagel
K Wiedemann
M N Smolka
A Heinz
M Rietschel
K Mann
机构：
[1] Central Institute of Mental Health,Department of Addictive Behavior and Addiction Medicine
[2] Central Institute of Mental Health,Department of Genetic Epidemiology in Psychiatry
[3] Life & Brain Center,Department of Genomics
[4] University of Bonn,Department of Psychiatry & Psychotherapy
[5] Institute of Human Genetics,Department of Psychiatry & Psychotherapy
[6] University of Bonn,Department of Psychiatry
[7] University of Tübingen,Department of Psychiatry and Psychotherapy
[8] University of Freiburg,Department of Psychopharmacology
[9] Psychosomatics and Psychotherapy,Department of Psychiatry and Psychotherapy
[10] University Medical Center Regensburg,Department of Psychiatry and Psychotherapy
[11] University Hospital Carl Gustav Carus,undefined
[12] Technische Universität Dresden,undefined
[13] Central Institute of Mental Health,undefined
[14] University Hospital Hamburg-Eppendorf,undefined
[15] CCM,undefined
[16] Charité University Medicine,undefined
来源：
The Pharmacogenomics Journal | 2011年 / 11卷
关键词：
genetic association study; alcohol; GATA4; atrial natriuretic peptide; acamprosate;
D O I：
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学科分类号：
摘要：
In alcoholism, both relapse to alcohol drinking and treatment response are suggested to be genetically modulated. This study set out to determine whether the top 15 single nucleotide polymorphisms (SNPs) of a recent genome-wide association (GWA) and follow-up study of alcohol dependence are associated with relapse behavior and pharmacological treatment response in 374 alcohol-dependent subjects who underwent a randomized, double-blind, placebo-controlled trial with acamprosate, naltrexone or placebo. The single nucleotide polymorphism, rs13273672, an intronic SNP in the gene for GATA-binding protein 4 (GATA4), was associated with relapse within the 90-day medical treatment period (P<0.01). Subsequent pharmacogenetic analyses showed that this association was mainly based on patients treated with acamprosate (P<0.01). In line with the observation that natriuretic peptide promoters are modulated by GATA4, a significant gene dose effect on the variance of atrial natriuretic peptide (ANP) plasma concentration in the different GATA4 genotypes (P<0.01) was found. Hence, genetic variations in GATA4 might influence relapse and treatment response to acamprosate in alcohol-dependent patients via modulation of ANP plasma levels. These results could help to identify those alcohol-dependent patients who may be at an increased risk of relapse and who may better respond to treatment with acamprosate.
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页码：368 / 374
页数：6
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