Gene-Diet Interactions in High-Density Lipoprotein Cholesterol-Related Polymorphisms and Cardiovascular Disease Risk: Insights from the Korean Genome and Epidemiology Study

Abstract

Background: Understanding gene-diet interactions is crucial for establishing dietary guidelines for cardiovascular diseases (CVD). This study analyzed the interaction between dietary intake and six genome-wide association study (GWAS)-identified single nucleotide polymorphisms (SNP) associated with high-density lipoprotein (HDL) cholesterol levels and their impact on CVD risk. Methods: A total of 68,806 participants in the Korean Genome and Epidemiology Study (KoGES) were analyzed. Six target SNPs (LPL: rs17482753; ABCA1: rs1883025; APOA5: rs651821; LIPC: rs1077835; CETP: rs17231506; and LIPG: rs9953437) were extracted from genome-wide SNP genotype data. Dietary intake was assessed using a food frequency questionnaire. SNP genotyping was conducted using the Korea Biobank Array (Korean Chip), a specialized genotyping platform designed for GWAS of blood biochemical traits in the Korean population. SNP-diet interactions on CVD risk were analyzed using generalized linear models (GLM). Results: Among the six SNPs, ABCA1: rs1883025 and APOA5: rs651821 showed significant gene-diet interactions. For rs1883025 (ABCA1), carriers of the T allele exhibited reduced HDL cholesterol levels. However, in the high-protein intake group, individuals with the T/T genotype had a significantly lower risk of ischemic stroke compared to those in the low-protein intake group (interaction p-value = 0.044). For rs651821 (APOA5), carriers of the T allele also had lower HDL cholesterol levels, but individuals with the C/C genotype (wild-type homozygotes) in the low-fat intake group showed a significantly reduced risk of coronary artery disease (interaction p-value = 0.0155). Conclusions: This study suggests potential interactions between polymorphisms associated with low HDL cholesterol and dietary patterns, particularly high-protein and low-fat diets, in relation to CVD risk. These findings highlight the importance of personalized dietary recommendations based on genetic profiles to reduce CVD risk. They provide a basis for future research aimed at developing precision nutrition guidelines and targeted interventions to manage hypo-HDL cholesterolemia and nutrition-related CVD risks.