Associations Between <i>APOE</i> Gene Variants and Metabolite Levels in Hypercholesterolemia: A Metabolite GWAS Study in a Korean Cohor

Hypercholesterolemia, a form of hyperlipidemia, is a significant risk factor for cardiovascular diseases, often linked to genetic variations in the APOE gene, particularly the 4 allele, which influences LDL cholesterol levels.This study aimed to examine the association between APOE gene variants and plasma sphingomyelin levels in Korean individuals with hypercholesterolemia, using a metabolite genome-wide association study (mGWAS) approach.Data from 7,031 participants in the Korean Genome and Epidemiology Study (KoGES) were analyzed.Genetic associations with cholesterol and sphingomyelin levels were evaluated through Exome chip analysis and metabolite profiling.Significant associations were identified between specific APOE variants (e.g., rs769449, rs4420638) and serum cholesterol levels.Additionally, certain SNPs were linked to variations in plasma sphingomyelin levels, suggesting a genetic influence on both lipid and sphingomyelin metabolism.The findings underscore the relevance of mGWAS in unraveling the genetic and metabolic pathways involved in hypercholesterolemia, offering potential biomarkers for disease risk and therapeutic targets.