Investigation of 95 variants identified in a genome-wide study for association with mortality after acute coronary syndrome

BMC Medical Genetics

Research Article

Bernhard R Winkelmann¹  Stanley L Hazen²  Sharon Cresci³  Thomas M Morgan⁴  Harlan M Krumholz⁵  Hooman Allayee⁵  Yesha Patel⁵  Bernhard O Boehm⁶  Arshed A Quyyumi⁷  Danny J Eapen⁷  Riyaz S Patel⁸  Marcus E Kleber⁹  Salina P Waddy^1,10  John A House^1,11  Philip Jones^1,11  John A Spertus^1,11  Winfried März^1,12 

[1] Cardiology Group Sachenhausen, Frankfurt Sachsenhausen, Germany;Center for Cardiovascular Diagnostics and Prevention, Department of Cell Biology, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA;Department of Internal Medicine, Cardiovascular Division, Washington University School of Medicine, St. Louis, MO, USA;Department of Pediatrics, Vanderbilt University School of Medicine, Nashville, TN, USA;Department of Preventive Medicine, USC Keck School of Medicine, Los Angeles, CA, USA;Division of Endocrinology, Diabetes and Metabolism, Graduate School of Molecular Diabetology and Endocrinology, Ulm University, Germany, 13Robert Wood Johnson Clinical Scholars Program and Department of Internal Medicine, Yale University School of Medicine, New Haven, CT, USA;Emory University School of Medicine, Atlanta, GA, USA;Emory University School of Medicine, Atlanta, GA, USA;Cardiff University, Cardiff, Wales, UK;LURIC non profit LLC, Freiburg im Breisgau, Germany, and Mannheim Institute of Public Health, Medical Faculty Mannheim, University of Heidelberg, Germany;NINDS/NIH, Bethesda, MD, USA;Saint Luke's Mid America Heart Institute and University of Missouri-Kansas City, Kansas City, MO, USA;synlab Services GmbH, Mannheim, and Mannheim Institute of Public Health, Medical Faculty Mannheim, University of Heidelberg, Germany, and Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Austria;

关键词: Acute Coronary Syndrome;    Acute Coronary Syndrome Patient;    Wellcome Trust Case Control Consortium;    Replication Cohort;    Acute Coronary Syndrome Risk;   

DOI  :  10.1186/1471-2350-12-127

 received in 2010-10-27, accepted in 2011-09-29,  发布年份 2011

来源: Springer

【 摘 要 】

BackgroundGenome-wide association studies (GWAS) have identified new candidate genes for the occurrence of acute coronary syndrome (ACS), but possible effects of such genes on survival following ACS have yet to be investigated.MethodsWe examined 95 polymorphisms in 69 distinct gene regions identified in a GWAS for premature myocardial infarction for their association with post-ACS mortality among 811 whites recruited from university-affiliated hospitals in Kansas City, Missouri. We then sought replication of a positive genetic association in a large, racially diverse cohort of myocardial infarction patients (N = 2284) using Kaplan-Meier survival analyses and Cox regression to adjust for relevant covariates. Finally, we investigated the apparent association further in 6086 additional coronary artery disease patients.ResultsAfter Cox adjustment for other ACS risk factors, of 95 SNPs tested in 811 whites only the association with the rs6922269 in MTHFD1L was statistically significant, with a 2.6-fold mortality hazard (P = 0.007). The recessive A/A genotype was of borderline significance in an age- and race-adjusted analysis of the entire combined cohort (N = 3095; P = 0.052), but this finding was not confirmed in independent cohorts (N = 6086).ConclusionsWe found no support for the hypothesis that the GWAS-identified variants in this study substantially alter the probability of post-ACS survival. Large-scale, collaborative, genome-wide studies may be required in order to detect genetic variants that are robustly associated with survival in patients with coronary artery disease.

【 授权许可】

CC BY   
© Morgan et al; licensee BioMed Central Ltd. 2011