title: The Effect of FLT1 Variant on Long-Term Cardiovascular Outcomes: Validation of a Locus Identified in a Previous Genome-Wide Association Study.
abstract: 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.
authors.affiliation: Division of Cardiology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea.|Cardiovascular Research Institute and Cardiovascular Genome Center, Yonsei College of Medicine, Seoul, Korea.
authors.forename: Chan Joo
authors.initials: CJ
authors.lastname: Lee
authors.affiliation: Cardiovascular Research Institute and Cardiovascular Genome Center, Yonsei College of Medicine, Seoul, Korea.
authors.forename: Ji-Young
authors.initials: JY
authors.lastname: Lee
authors.affiliation: Department of Biostatistics and Computing, the Graduate School, Yonsei University, Seoul, Korea.
authors.forename: Chi-Yoon
authors.initials: CY
authors.lastname: Oum
authors.affiliation: Division of Cardiology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea.|Cardiovascular Research Institute and Cardiovascular Genome Center, Yonsei College of Medicine, Seoul, Korea.
authors.forename: Jong-Chan
authors.initials: JC
authors.lastname: Youn
authors.affiliation: Division of Cardiology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea.|Cardiovascular Research Institute and Cardiovascular Genome Center, Yonsei College of Medicine, Seoul, Korea.
authors.forename: Seok-Min
authors.initials: SM
authors.lastname: Kang
authors.affiliation: Division of Cardiology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea.|Cardiovascular Research Institute and Cardiovascular Genome Center, Yonsei College of Medicine, Seoul, Korea.
authors.forename: Donghoon
authors.initials: D
authors.lastname: Choi
authors.affiliation: Division of Cardiology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea.|Cardiovascular Research Institute and Cardiovascular Genome Center, Yonsei College of Medicine, Seoul, Korea.
authors.forename: Yangsoo
authors.initials: Y
authors.lastname: Jang
authors.affiliation: Division of Cardiology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea.|Cardiovascular Research Institute and Cardiovascular Genome Center, Yonsei College of Medicine, Seoul, Korea.
authors.forename: Sungha
authors.initials: S
authors.lastname: Park
authors.affiliation: Institute of Health Promotion, Graduate School of Public Health, Yonsei University, Seoul, Korea.
authors.forename: Sun Ha
authors.initials: SH
authors.lastname: Jee
authors.affiliation: Division of Cardiology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea.|Cardiovascular Research Institute and Cardiovascular Genome Center, Yonsei College of Medicine, Seoul, Korea.
authors.forename: Sang-Hak
authors.initials: SH
authors.lastname: Lee
mesh_terms: D000368:Aged; D000483:Alleles; D044466:Asian People / Q000235:genetics; D002899:Chromosomes, Human, Pair 9; D003324:Coronary Artery Disease / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D005260:Female; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D016016:Proportional Hazards Models; D056910:Republic of Korea; D012307:Risk Factors; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000235:genetics*
chemical_list: C501162:FLT1 protein, human; D040281:Vascular Endothelial Growth Factor Receptor-1