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

Authors
 Chan Joo Lee  ;  Ji-Young Lee  ;  Chi-Yoon Oum  ;  Jong-Chan Youn  ;  Seok-Min Kang  ;  Donghoon Choi  ;  Yangsoo Jang  ;  Sungha Park  ;  Sun Ha Jee  ;  Sang-Hak Lee 
Citation
 PLoS One, Vol.11(10) : e0164705, 2016 
Journal Title
 PLoS One 
Issue Date
2016
MeSH
Aged ; Alleles ; Asian Continental Ancestry Group/genetics ; Chromosomes, Human, Pair 9 ; Coronary Artery Disease/genetics* ; Coronary Artery Disease/mortality ; Coronary Artery Disease/pathology ; Female ; Genome-Wide Association Study ; Genotype ; Humans ; Kaplan-Meier Estimate ; Male ; Middle Aged ; Polymorphism, Single Nucleotide ; Proportional Hazards Models ; Republic of Korea ; Risk Factors ; Vascular Endothelial Growth Factor Receptor-1/genetics*
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.
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DOI
10.1371/journal.pone.0164705
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
4. Graduate School of Public Health (보건대학원) > Graduate School of Public Health (보건대학원) > 1. Journal Papers
Yonsei Authors
강석민(Kang, Seok Min) ORCID logo https://orcid.org/0000-0001-9856-9227
박성하(Park, Sung Ha) ORCID logo https://orcid.org/0000-0001-5362-478X
이상학(Lee, Sang Hak) ORCID logo https://orcid.org/0000-0002-4535-3745
이찬주(Lee, Chan Joo) ORCID logo https://orcid.org/0000-0002-8756-409X
장양수(Jang, Yang Soo) ORCID logo https://orcid.org/0000-0002-2169-3112
지선하(Jee, Sun Ha) ORCID logo https://orcid.org/0000-0001-9519-3068
최동훈(Choi, Dong Hoon) ORCID logo https://orcid.org/0000-0002-2009-9760
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URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/152338
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