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

• Main Authors: Winkelmann Bernhard R (Author), März Winfried (Author), Kleber Marcus E (Author), Quyyumi Arshed A (Author), Waddy Salina P (Author), Eapen Danny J (Author), Patel Riyaz S (Author), Patel Yesha (Author), Hazen Stanley L (Author), Allayee Hooman (Author), Jones Philip (Author), Cresci Sharon (Author), Morgan Thomas M (Author), House John A (Author), Boehm Bernhard O (Author), Krumholz Harlan M (Author), Spertus John A (Author)
• Format: Book
• Published: BMC, 2011-09-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.

Summary

<p>Abstract</p> <p>Background</p> <p>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.</p> <p>Methods</p> <p>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.</p> <p>Results</p> <p>After Cox adjustment for other ACS risk factors, of 95 SNPs tested in 811 whites only the association with the rs6922269 in <it>MTHFD1L </it>was statistically significant, with a 2.6-fold mortality hazard (<it>P </it>= 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; <it>P </it>= 0.052), but this finding was not confirmed in independent cohorts (N = 6086).</p> <p>Conclusions</p> <p>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.</p>

Item Description

10.1186/1471-2350-12-127
1471-2350