title: Involvement of the atrial natriuretic peptide transcription factor GATA4 in alcohol dependence, relapse risk and treatment response to acamprosate.
abstract: 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.
authors.affiliation: Department of Addictive Behavior and Addiction Medicine, Central Institute of Mental Health, Mannheim, Germany. falk.kiefer@zi-mannheim.de
authors.forename: F
authors.initials: F
authors.lastname: Kiefer
authors.forename: S H
authors.initials: SH
authors.lastname: Witt
authors.forename: J
authors.initials: J
authors.lastname: Frank
authors.forename: A
authors.initials: A
authors.lastname: Richter
authors.forename: J
authors.initials: J
authors.lastname: Treutlein
authors.forename: T
authors.initials: T
authors.lastname: Lemenager
authors.forename: M M
authors.initials: MM
authors.lastname: Nöthen
authors.forename: S
authors.initials: S
authors.lastname: Cichon
authors.forename: A
authors.initials: A
authors.lastname: Batra
authors.forename: M
authors.initials: M
authors.lastname: Berner
authors.forename: N
authors.initials: N
authors.lastname: Wodarz
authors.forename: U S
authors.initials: US
authors.lastname: Zimmermann
authors.forename: R
authors.initials: R
authors.lastname: Spanagel
authors.forename: K
authors.initials: K
authors.lastname: Wiedemann
authors.forename: M N
authors.initials: MN
authors.lastname: Smolka
authors.forename: A
authors.initials: A
authors.lastname: Heinz
authors.forename: M
authors.initials: M
authors.lastname: Rietschel
authors.forename: K
authors.initials: K
authors.lastname: Mann
mesh_terms: D000077443:Acamprosate; D000328:Adult; D000427:Alcohol Deterrents / Q000627:therapeutic use*; D000437:Alcoholism / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D000438:Alcohols / Q000378:metabolism*; D009320:Atrial Natriuretic Factor / Q000097:blood / Q000235:genetics*; D005260:Female; D050991:GATA4 Transcription Factor / Q000235:genetics* / Q000378:metabolism; D018628:Gene Dosage; D056726:Genetic Association Studies; D014644:Genetic Variation; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D016032:Randomized Controlled Trials as Topic; D012008:Recurrence; D012306:Risk; D013654:Taurine / Q000031:analogs & derivatives* / Q000235:genetics / Q000627:therapeutic use
chemical_list: D000427:Alcohol Deterrents; D000438:Alcohols; D050991:GATA4 Transcription Factor; C484170:GATA4 protein, human; D013654:Taurine; D009320:Atrial Natriuretic Factor; D000077443:Acamprosate