Impact of Genetic Markers related to Hyper-HDL Cholesterol on the Prevalence of Myocardial Infarction: A KoGES study.

Abstract

Recent studies have shown that hyper-HDL-cholesterol (HDL-C) is associated with cardiovascular disease (CVD) 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 9 loci. We identified 6 SNPs significantly related to both hypo- and hyper-HDL groups, one SNP associated with hyper-HDL, and 6 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 serve as essential markers for detecting MI risk based on lipid profiles, pending replication in other cohorts.