Background: Data on genetic variants that can predict follow-up cardiovascular events are highly limited, particularly for Asians. The aim of this study was to validate the effects of two variants in FLT1 and 9p21 on long-term cardiovascular outcomes in high-risk Korean patients. Methods: We examined the prognostic values of the rs9508025 and rs1333049 variants that were found to be associated with coronary artery disease (CAD) risk in a previous Korean genome-wide association study. A total of 2693 patients (mean age: 55.2 years; male: 55.2%) with CAD or its risk factors at baseline were enrolled and followed for major adverse cardiac events (MACE). Results: During the mean follow-up of 8.8 years, 15.4% of the patients experienced MACE. Kaplan-Meier curves showed that MACE-free survival was different according to the genotype of rs9508025 (log rank p = 0.02), whereas rs1333049 genotype did not correlate with the prognosis. Multivariate Cox proportional hazard analysis showed that C-allele of rs9508025 was significantly associated with a high rate of MACE, while rs1333049 was not. Further analyses demonstrated that the association of the rs9508025 variant with MACE was mainly due to its relation to coronary revascularization, which was also associated with the rs1333049 variant. In an additional analysis, rs9508025 was found to be an independent determinant of the outcome only in the subgroup with history of CAD. Conclusions: rs9508025 in FLT1 was significantly associated with long-term cardiovascular events, particularly in patients with prior CAD. The association of rs1333049 in 9p21 was not significant.
Bibliographical noteFunding Information:
This research was financially supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science, and Technology (2012R1A4A1029061 and 2014R1A1A2056104), the Bio and Medical Technology Development Program of the NRF funded by the Korean government, MSIP (2015M3A9B6029138), and the Creative Allied Project (CAP) grant funded by the Korean Research Council of Fundamental Science and Technology (KRCF). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
© 2016 Lee et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
All Science Journal Classification (ASJC) codes
- Biochemistry, Genetics and Molecular Biology(all)
- Agricultural and Biological Sciences(all)