title: GNB3 gene 825 TT variant predicts hard coronary events in the population-based Heinz Nixdorf Recall study.
abstract: OBJECTIVE
  The C825T polymorphism of the gene encoding the human G protein beta-3 subunit (GNB3) is associated with hypertension and obesity. Moreover, genotypes of the GNB3 polymorphism have been associated with development of coronary artery disease, and the 825T allele is thought to influence the process of atherosclerosis. However, the potential of the C825T polymorphism to predict coronary events has been poorly explored in a longitudinal setting at the population level.
  
  
  METHODS
  In 4159 Caucasian subjects from the Heinz Nixdorf Recall study cohort (age: 45-75 years, 48% male), genotypes of the GNB3 C825T polymorphism (rs5443) were determined and associated with fatal and non-fatal myocardial infarction (hard coronary events). Established cardiovascular risk factors were used to adjust for confounders.
  
  
  RESULTS
  The median follow-up time was 9.9 years (1st/3rd quartiles 9.5/10.2). 148 subjects (3.6%) experienced a hard coronary event. The 10-year event-free survival rate was CC, 96.1%; CT 96.9%, TT, 93.7% (p = 0.018). Multivariable analysis showed that the TT genotype is a significant risk factor for hard coronary events (hazard ratio (HR) = 1.9 (95% confidence interval (CI) 1.2-2.9); p = 0.008) after adjustment for age, sex, diabetes, systolic blood pressure, body mass index, high-density lipoprotein, and coronary artery calcification as determined by electron beam computed tomography at baseline. While prognosis in females was independent of GNB3 genotypes, analysis in males even elevated the HR for TT versus C-allele to 2.6 (95% CI 1.6-4.2; p < 0.001).
  
  
  CONCLUSIONS
  The GNB3 825 TT genotype is a significant and independent risk factor for hard coronary events independent of other established cardiovascular risk factors at a population level in males.
authors.affiliation: Klinik für Anästhesiologie und Intensivmedizin, Universität Duisburg-Essen und Universitätsklinikum Essen, Essen, Germany. Electronic address: Ulrich.frey@uk-essen.de.
authors.forename: Ulrich H
authors.initials: UH
authors.lastname: Frey
authors.affiliation: Institut für medizinische Informatik, Biometrie und Epidemiologie, Universität Duisburg-Essen und Universitätsklinikum Essen, Essen, Germany.
authors.forename: Susanne
authors.initials: S
authors.lastname: Moebus
authors.affiliation: Medizinische Klinik II, Moers, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Möhlenkamp
authors.affiliation: Klinik für Kardiologie, Universität Duisburg-Essen und Universitätsklinikum Essen, Essen, Germany.
authors.forename: Hagen
authors.initials: H
authors.lastname: Kälsch
authors.affiliation: Klinik für Kardiologie, Universität Duisburg-Essen und Universitätsklinikum Essen, Essen, Germany.
authors.forename: Marcus
authors.initials: M
authors.lastname: Bauer
authors.affiliation: Institut für medizinische Informatik, Biometrie und Epidemiologie, Universität Duisburg-Essen und Universitätsklinikum Essen, Essen, Germany.
authors.forename: Nils
authors.initials: N
authors.lastname: Lehmann
authors.affiliation: Institut für Humangenetik, Universität Bonn, Germany; Abteilung für Genomik, Life & Brain GmbH, Universität Bonn, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Nöthen
authors.affiliation: Institut für Humangenetik, Universität Bonn, Germany; Abteilung für Genomik, Life & Brain GmbH, Universität Bonn, Germany.
authors.forename: Thomas W
authors.initials: TW
authors.lastname: Mühleisen
authors.affiliation: Institut für klinische Epidemiologie, Medizinische Fakultät, Martin-Luther-Universität Halle-Wittenberg, Halle, Germany; Department of Epidemiology, School of Public Health, Boston University, Boston, USA.
authors.forename: Andreas
authors.initials: A
authors.lastname: Stang
authors.affiliation: Klinik für Kardiologie, Universität Duisburg-Essen und Universitätsklinikum Essen, Essen, Germany.
authors.forename: Raimund
authors.initials: R
authors.lastname: Erbel
authors.affiliation: Medizinische Klinik II, Moers, Germany.
authors.forename: Karl-Heinz
authors.initials: KH
authors.lastname: Jöckel
authors.affiliation: Klinik für Anästhesiologie und Intensivmedizin, Universität Duisburg-Essen und Universitätsklinikum Essen, Essen, Germany.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Peters
authors.affiliation: Institut für Pharmakogenetik, Universität Duisburg-Essen und Universitätsklinikum Essen, Essen, Germany.
authors.forename: Winfried
authors.initials: W
authors.lastname: Siffert
mesh_terms: D000368:Aged; D000483:Alleles; D000818:Animals; D015415:Biomarkers / Q000097:blood; D001794:Blood Pressure; D003324:Coronary Artery Disease / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D005858:Germany; D020962:Heterotrimeric GTP-Binding Proteins / Q000235:genetics*; D006801:Humans; D006973:Hypertension / Q000235:genetics; D053208:Kaplan-Meier Estimate; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000235:genetics; D011110:Polymorphism, Genetic; D012307:Risk Factors; D012737:Sex Factors; D015398:Signal Transduction; D014057:Tomography, X-Ray Computed
chemical_list: D015415:Biomarkers; C000595803:GNB3 protein, human; D020962:Heterotrimeric GTP-Binding Proteins
keywords: Adrenergic signaling; Coronary artery disease; Genetics; Mortality; Outcome; Polymorphism; Signal transduction