Hur Haeng Jeon, Yang Hye Jeong, Kim Min Jung, Lee Kyunhee, Jang Dai Ja, Kim Myung-Sunny, Park Sunmin
Food Functionality Research Division, Korea Food Research Institute, Wanju-gun, Jeollabuk-do, Republic of Korea.
Department of Food Biotechnology, University of Science & Technology, Wanju-gun, Jeollabuk-do, Republic of Korea.
Front Nutr. 2023 Oct 4;10:1244185. doi: 10.3389/fnut.2023.1244185. eCollection 2023.
Hypo-high-density lipoprotein cholesterolemia (hypo-HDL-C) contributes to the development of cardiovascular diseases. The hypothesis that the polygenic variants associated with hypo-HDL-C interact with lifestyle factors was examined in 58,701 middle-aged Korean adults who participated in the Korean Genome and Epidemiology Study (KoGES).
Participants were categorized into the Low-HDL (case; = 16,980) and Normal-HDL ( = 41,721) groups. The participants in the Low-HDL group were selected using the guideline-based cutoffs for hypo-HDL-C (<40 mg/dL for men and < 50 mg/dL for women) and included those taking medication for dyslipidemia. The genes associated with hypo-HDL-C were determined through a genome-wide association study (GWAS) in a city hospital-based cohort, and the results were validated in the Ansan/Anung study. The genetic variants for the single nucleotide polymorphism (SNP)-SNP interaction were selected using a generalized multifactor dimensionality reduction analysis, and the polygenic risk score (PRS) generated was evaluated for interaction with lifestyle parameters.
The participants with hypo-HDL-C showed a 1.45 and 1.36-fold higher association with myocardial infarction and stroke, respectively. The High-PRS with four SNPs, namely _rs3741297, _rs708272, _rs180327, and _rs588136, and that with the 11q23.3 haplotype were positively associated with hypo-HDL-C by about 3 times, which was a 2.4-fold higher association than the PRS of 24 SNP with < 5×10. The risk alleles of _rs708272 and _rs588136 were linked to increased expression in the heart and decreased in the brain, respectively. The selected SNPs were linked to the reverse cholesterol transport pathway, triglyceride-rich lipoprotein particle remodeling pathway, cholesterol storage, and macrophage-derived foam cell differentiation regulation. The PRS of the 4-SNP model interacted with energy intake and smoking status, while that of the haplotype interacted with a glycemic index of the diet, sulfur microbial diet, and smoking status.
Adults with a genetic risk for hypo-HDL-C need to modulate their diet and smoking status to reduce their risk.
低高密度脂蛋白胆固醇血症（低HDL-C）会促使心血管疾病的发展。在参与韩国基因组与流行病学研究（KoGES）的58701名中年韩国成年人中，对与低HDL-C相关的多基因变异与生活方式因素相互作用的假设进行了研究。
参与者被分为低HDL组（病例组；n = 16980）和正常HDL组（n = 41721）。低HDL组的参与者根据基于指南的低HDL-C临界值（男性<40mg/dL，女性<50mg/dL）进行选择，包括正在服用血脂异常药物的患者。通过在一家城市医院队列中进行的全基因组关联研究（GWAS）确定与低HDL-C相关的基因，并在安山/阿农研究中对结果进行验证。使用广义多因素降维分析选择单核苷酸多态性（SNP）-SNP相互作用的遗传变异，并评估所产生的多基因风险评分（PRS）与生活方式参数的相互作用。
低HDL-C参与者发生心肌梗死和中风的关联分别高1.45倍和1.36倍。含有四个SNP（即_rs3741297、_rs708272、_rs180327和_rs588136）的高PRS以及含有11q23.3单倍型的高PRS与低HDL-C呈正相关，约为3倍，这比24个SNP（<5×10）的PRS关联高2.4倍。_rs708272和_rs588136的风险等位基因分别与心脏中表达增加和大脑中表达减少有关。所选的SNP与逆向胆固醇转运途径、富含甘油三酯的脂蛋白颗粒重塑途径、胆固醇储存以及巨噬细胞衍生的泡沫细胞分化调节有关。4-SNP模型的PRS与能量摄入和吸烟状况相互作用，而单倍型的PRS与饮食的血糖指数、含硫微生物饮食和吸烟状况相互作用。
具有低HDL-C遗传风险的成年人需要调整饮食和吸烟状况以降低风险。
