Home
Deutsch
Advanced Search
Browse by ...
Publication overview
Contact persons
Help
DOI
PMC
 |
|
Open Access Green as soon as Postprint is submitted to ZB.
GNAS gene variants affect β-blocker-related survival after coronary artery bypass grafting.
Anesthesiology 120, 1109-1117 (2014)
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.
Altmetric
Additional Metrics?
Edit extra informations
Login
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
ISSN (print) / ISBN
0003-3022
e-ISSN
1528-1175
Journal
Anesthesiology
Quellenangaben
Volume: 120,
Issue: 5,
Pages: 1109-1117
Publisher
Lippincott Williams & Wilkins
Publishing Place
Philadelphia
Non-patent literature
Publications
Reviewing status
Peer reviewed
Institute(s)
Institute of Human Genetics (IHG)