The effect of FLT1 variant on long-term cardiovascular outcomes

Validation of a locus identified in a previous genome-wide association study

Chan Joo Lee, Ji Young Lee, Chi Yoon Oum, Jong Chan Youn, seokmin kang, Donghoon Choi, Yangsoo Jang, Sungha Park, Sun Ha Jee, Sang Hak Lee

Research output: Contribution to journalArticle

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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.

Original languageEnglish
Article numbere0164705
JournalPLoS ONE
Volume11
Issue number10
DOIs
Publication statusPublished - 2016 Oct 1

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Genome-Wide Association Study
Coronary Artery Disease
Genes
loci
Genotype
hazard characterization
genotype
prognosis
Disease-Free Survival
Hazards
risk factors
Alleles
alleles
genome-wide association study
coronary artery disease
methodology

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

@article{3dd4e6cf915d44669c8bbc8132e358b7,
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.",
author = "Lee, {Chan Joo} and Lee, {Ji Young} and Oum, {Chi Yoon} and Youn, {Jong Chan} and seokmin kang and Donghoon Choi and Yangsoo Jang and Sungha Park and Jee, {Sun Ha} and Lee, {Sang Hak}",
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month = "10",
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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. / Lee, Chan Joo; Lee, Ji Young; Oum, Chi Yoon; Youn, Jong Chan; kang, seokmin; Choi, Donghoon; Jang, Yangsoo; Park, Sungha; Jee, Sun Ha; Lee, Sang Hak.

In: PLoS ONE, Vol. 11, No. 10, e0164705, 01.10.2016.

Research output: Contribution to journalArticle

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T1 - The effect of FLT1 variant on long-term cardiovascular outcomes

T2 - Validation of a locus identified in a previous genome-wide association study

AU - Lee, Chan Joo

AU - Lee, Ji Young

AU - Oum, Chi Yoon

AU - Youn, Jong Chan

AU - kang, seokmin

AU - Choi, Donghoon

AU - Jang, Yangsoo

AU - Park, Sungha

AU - Jee, Sun Ha

AU - Lee, Sang Hak

PY - 2016/10/1

Y1 - 2016/10/1

N2 - 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.

AB - 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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