PuSH - Publication Server of Helmholtz Zentrum München

Export: TXT Text RIS Endnote (RIS) BIB BibTeX
Frey, U.H.* ; Muehlschlegel, J.D.* ; Ochterbeck, C.* ; Fox, A.A.* ; Shernan, S.K.* ; Collard, C.D.* ; Lichtner, P. ; Peters, J.* ; Body, S.*

GNAS gene variants affect β-blocker-related survival after coronary artery bypass grafting.

Anesthesiology 120, 1109-1117 (2014)
Publ. Version/Full Text Volltext DOI PMC
Open Access Gold
BACKGROUND: Cardiac overexpression of the β-adrenoreceptor (βAR)-coupled stimulatory G-protein subunit Gαs enhances inotropic responses to adrenergic stimulation and improves survival in mice under βAR blockade. The authors recently identified three common haplotypes in the GNAS gene encoding Gαs, with the greatest Gαs protein expression and signal transduction in haplotype *3 carriers and less in haplotype *2 and *1 carriers. The authors tested the hypothesis that these GNAS variants result in altered mortality in patients after coronary artery bypass graft surgery, particularly in those receiving βAR blockade. METHODS: This prospective analysis included 1,627 European ancestry patients undergoing primary coronary artery bypass graft surgery. Patients were genotyped for two GNAS haplotype tagging single-nucleotide polymorphisms defining three major haplotypes. Up to 5-yr all-cause mortality was estimated using a Cox proportional hazard model; hazard ratios and 95% CIs were calculated while adjusting for demographics, clinical covariates, and the new EuroSCORE II. RESULTS: Univariate analysis revealed haplotype-dependent 5-yr mortality rates (*1/*1: 18.9%, *2/*1: 13.7%, *2/*2: 9.3%, *3/*1: 10.6%, *3/*2: 9.1%, and *3/*3: 9.6%; P = 0.0006). After adjustment for other predictors of death, homozygote haplotype *1 carriers showed a doubled risk for death (hazard ratio, 2.2; 95% CI, 1.2 to 3.8; P = 0.006). Considering only patients receiving βAR blockers (n = 1,267), the adjusted risk of death even tripled (hazard ratio, 3.0; 95% CI, 1.5 to 6.1; P = 0.002). CONCLUSIONS: GNAS haplotypes independently associate with an increased risk of death after primary coronary artery bypass graft surgery. These results are most pronounced in patients receiving βAR blockers, strengthening the rationale for personalized treatment, to decrease medication side effects and improve outcomes.
Impact Factor
Scopus SNIP
Web of Science
Times Cited
Scopus
Cited By
Altmetric
6.168
2.506
4
6
Tags
Annotations
Special Publikation
Hide on homepage

Edit extra information
Edit own tags
Private
Edit own annotation
Private
Hide on publication lists
on hompage
Mark as special
publikation
Publication type Article: Journal article
Document type Scientific Article
Keywords G-alpha-s; Heart-failure; Myocardial-infarction; Ventricular Dysfunction; Independent Predictor; Cardiac-function; Controlled-trial; Euroscore Ii; G-proteins; Surgery
Language english
Publication Year 2014
HGF-reported in Year 2014
ISSN (print) / ISBN 0003-3022
e-ISSN 1528-1175
Journal Anesthesiology
Quellenangaben Volume: 120, Issue: 5, Pages: 1109-1117 Article Number: , Supplement: ,
Publisher Lippincott Williams & Wilkins
Publishing Place Philadelphia
Reviewing status Peer reviewed
Institute(s) Institute of Human Genetics (IHG)
POF-Topic(s) 30501 - Systemic Analysis of Genetic and Environmental Factors that Impact Health
Research field(s) Genetics and Epidemiology
PSP Element(s) G-500700-001
PubMed ID 24755784
DOI 10.1097/ALN.0000000000000189
WOS ID WOS:000335175100010
Scopus ID 84899093946
Erfassungsdatum 2014-04-25
[➜Report correction]