The Effect of FLT1 Variant on Long-Term Cardiovascular Outcomes: Validation of a Locus Identified in a Previous Genome-Wide Association Study

Abstract

BackgroundData 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.MethodsWe 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).ResultsDuring 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.Conclusionsrs9508025 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.

Complex Evaluation of the Significance of Populational Genetic Markers Associated With Myocardial Infarction and Risk Factors

“…До сих пор, спустя 10 лет после первой публикации, нет еди-ного мнения о вкладе в риск развития ИБС даже локуса 9p21. Так, в Корее в 2008г Shen GQ, et al пока-зали ассоциацию локуса 9p21 с ИБС, однако в 2016г Lee CJ, et al пришли к выводу, что при проспектив-ном наблюдении маркер rs1333049 оказался не свя-занным с исходами [8]. Кроме того, до сих пор неясны механизмы реализации замен в нуклеотидной после-довательности этого участка ДНК в патологический фенотип.…”