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

Background: Genome-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 inve
Background: Genome-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.
Methods: We 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.
Results: After 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).
Conclusions: We 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.
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  • Tables S1-S3. Description of additional study populations. Genotyping methods in additional study populations. Supplemental results in additional study populations. Supplemental Table 1. Supplemental Table 2. Supplemental Table 3.

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Author:Thomas M. Morgan, John A. House, Hooman Allayee, Sharon Cresci, Philip Jones, Stanley L. Hazen, Yesha Patel, Riyaz S. Patel, Danny J. Eapen, Salina P. Waddy, Arshed A. Quyyumi, Marcus E. Kleber, Winfried März, Bernhard R. Winkelmann, Bernhard O. Böhm, Harlan M. Krumholz, John A. Spertus
URN:urn:nbn:de:hebis:30:3-228759
DOI:http://dx.doi.org/doi:10.1186/1471-2350-12-127
ISSN:1471-2350
Parent Title (English):BMC medical genetics
Publisher:BioMed Central
Place of publication:London
Document Type:Article
Language:English
Year of Completion:2011
Date of first Publication:2011/09/29
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2011/07/18
Volume:12
Issue:127
Pagenumber:7
First Page:1
Last Page:7
Note:
© 2011 Morgan et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
HeBIS PPN:27989371X
Dewey Decimal Classification:610 Medizin und Gesundheit
Licence (German):License LogoCreative Commons - Namensnennung 2.0

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