Impact of genetic markers related to hyper-HDL cholesterol on the prevalence of myocardial infarction: a KoGES study

Recent studies have shown that hyper-high-density lipoprotein cholesterol (HDL-C) is associated with cardiovascular disease risk and all-cause mortality, a phenomenon known as the HDL-C paradox. Several genes have been reported to show relationships between increased HDL-C and myocardial infarction...

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Main Authors: Sung-Bum Lee, Kyung-Won Hong, Byoungjin Park, Dong-Hyuk Jung
Format: Article
Language:English
Published: Elsevier 2025-04-01
Series:Journal of Lipid Research
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Online Access:http://www.sciencedirect.com/science/article/pii/S0022227525000379
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author Sung-Bum Lee
Kyung-Won Hong
Byoungjin Park
Dong-Hyuk Jung
author_facet Sung-Bum Lee
Kyung-Won Hong
Byoungjin Park
Dong-Hyuk Jung
author_sort Sung-Bum Lee
collection DOAJ
description Recent studies have shown that hyper-high-density lipoprotein cholesterol (HDL-C) is associated with cardiovascular disease risk and all-cause mortality, a phenomenon known as the HDL-C paradox. Several genes have been reported to show relationships between increased HDL-C and myocardial infarction (MI) risk. We investigated the genetic predisposition of lipid metabolism influencing MI. The study dataset was from the Korean Genome and Epidemiology cohort obtained from the National Biobank of Korea, with an initial population of 68,806 individuals. We categorized samples based on HDL-C levels into hypo-HDL-C (n = 25,884), normal-HDL-C (n = 41,117), and hyper-HDL-C groups (n = 1,805). We conducted genome-wide association studies for each group and the total sample. Significant associations were defined using genome-wide significant level and suggestive level. The lead SNP of each locus was selected for further interpretation. This analysis included 2,014 (2.6%) MI patients. Using multivariable logistic regression, we evaluated the association of 7,877 SNPs in nine loci. We identified six SNPs significantly related to both hypo- and hyper-HDL groups, one SNP associated with hyper-HDL, and six SNPs associated with hypo-HDL group. Additionally, we found three SNPs associated with MI prevalence in the hyper-HDL group, including one significant SNP and two suggestive SNPs. Contrary to the traditional view of HDL-C as protective, this study identified genetic variants that increase MI risk by more than six-fold. These SNPs could play a role as important markers for detecting MI in hyper-HDL cholesterol group.
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spelling doaj-art-30ff3860fb0241d38a99efd93ae86e482025-08-20T02:12:07ZengElsevierJournal of Lipid Research0022-22752025-04-0166410077710.1016/j.jlr.2025.100777Impact of genetic markers related to hyper-HDL cholesterol on the prevalence of myocardial infarction: a KoGES studySung-Bum Lee0Kyung-Won Hong1Byoungjin Park2Dong-Hyuk Jung3Department of Family Medicine, Soonchunhyang University Bucheon Hospital, Bucheon, Republic of KoreaInstitute of Advanced Technology, THERAGEN HEALTH Co., Ltd., Seongnam-si, Gyeonggi-do, Republic of KoreaDepartment of Family Medicine, Yongin Severance Hospital, Yongin-si, Republic of KoreaDepartment of Family Medicine, Yongin Severance Hospital, Yongin-si, Republic of Korea; For correspondence: Dong-Hyuk JungRecent studies have shown that hyper-high-density lipoprotein cholesterol (HDL-C) is associated with cardiovascular disease risk and all-cause mortality, a phenomenon known as the HDL-C paradox. Several genes have been reported to show relationships between increased HDL-C and myocardial infarction (MI) risk. We investigated the genetic predisposition of lipid metabolism influencing MI. The study dataset was from the Korean Genome and Epidemiology cohort obtained from the National Biobank of Korea, with an initial population of 68,806 individuals. We categorized samples based on HDL-C levels into hypo-HDL-C (n = 25,884), normal-HDL-C (n = 41,117), and hyper-HDL-C groups (n = 1,805). We conducted genome-wide association studies for each group and the total sample. Significant associations were defined using genome-wide significant level and suggestive level. The lead SNP of each locus was selected for further interpretation. This analysis included 2,014 (2.6%) MI patients. Using multivariable logistic regression, we evaluated the association of 7,877 SNPs in nine loci. We identified six SNPs significantly related to both hypo- and hyper-HDL groups, one SNP associated with hyper-HDL, and six SNPs associated with hypo-HDL group. Additionally, we found three SNPs associated with MI prevalence in the hyper-HDL group, including one significant SNP and two suggestive SNPs. Contrary to the traditional view of HDL-C as protective, this study identified genetic variants that increase MI risk by more than six-fold. These SNPs could play a role as important markers for detecting MI in hyper-HDL cholesterol group.http://www.sciencedirect.com/science/article/pii/S0022227525000379myocardial infarctionhyper-HDL cholesterolSNPGWASKoGES
spellingShingle Sung-Bum Lee
Kyung-Won Hong
Byoungjin Park
Dong-Hyuk Jung
Impact of genetic markers related to hyper-HDL cholesterol on the prevalence of myocardial infarction: a KoGES study
Journal of Lipid Research
myocardial infarction
hyper-HDL cholesterol
SNP
GWAS
KoGES
title Impact of genetic markers related to hyper-HDL cholesterol on the prevalence of myocardial infarction: a KoGES study
title_full Impact of genetic markers related to hyper-HDL cholesterol on the prevalence of myocardial infarction: a KoGES study
title_fullStr Impact of genetic markers related to hyper-HDL cholesterol on the prevalence of myocardial infarction: a KoGES study
title_full_unstemmed Impact of genetic markers related to hyper-HDL cholesterol on the prevalence of myocardial infarction: a KoGES study
title_short Impact of genetic markers related to hyper-HDL cholesterol on the prevalence of myocardial infarction: a KoGES study
title_sort impact of genetic markers related to hyper hdl cholesterol on the prevalence of myocardial infarction a koges study
topic myocardial infarction
hyper-HDL cholesterol
SNP
GWAS
KoGES
url http://www.sciencedirect.com/science/article/pii/S0022227525000379
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