Division of Cardiology, Department of Internal Medicine, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea.
Department of Biomedical Science and Technology, Graduate School, Kyung Hee University, Seoul, Korea.
Sci Rep. 2019 Jul 29;9(1):10915. doi: 10.1038/s41598-019-47456-2.
The concentration of high-density lipoprotein-cholesterol (HDL-C) in humans is partially determined by genetic factors; however, the role of these factors is incompletely understood. The aim of this study was to examine the prevalence and characteristics of CETP, LIPC, and SCARB1 variants in Korean individuals with extremely high HDL-C levels. We also analysed associations between these variants and cholesterol efflux capacity (CEC), reactive oxygen species (ROS) generation, and vascular cell adhesion molecule-1 (VCAM-1) expression. Of 13,545 participants in the cardiovascular genome cohort, 42 subjects with HDL-C levels >100 mg/dL were analysed. The three target genes were sequenced by targeted next-generation sequencing, the functional effects of detected variants were predicted, and CEC was assessed using a radioisotope and apolipoprotein B-depleted sera. We observed two rare variants of CETP in 13 individuals (rare variant c.A1196G [p.D399G] of CETP was discovered in 12 subjects) and one rare variant of SCARB1 in one individual. Furthermore, all subjects had at least one of four common variants (one CETP and three LIPC variants). Two additional novel CETP variants of unknown frequency were found in two subjects. However, the identified variants did not show significant associations with CEC, ROS generation, or VCAM-1 expression. Our study provides additional insights into the role of genetics in individuals with extremely high HDL-C.
高密度脂蛋白胆固醇（HDL-C）在人体内的浓度部分由遗传因素决定；然而，这些因素的作用尚未完全了解。本研究旨在研究韩国超高 HDL-C 水平个体中 CETP、LIPC 和 SCARB1 变体的流行率和特征。我们还分析了这些变体与胆固醇流出能力（CEC）、活性氧（ROS）生成和血管细胞黏附分子-1（VCAM-1）表达之间的关联。在心血管基因组队列的 13545 名参与者中，分析了 42 名 HDL-C 水平>100mg/dL 的个体。通过靶向下一代测序对三个目标基因进行测序，预测检测到的变体的功能效应，并使用放射性同位素和载脂蛋白 B 耗尽的血清评估 CEC。我们在 13 名个体中观察到两种 CETP 罕见变体（CETP 的罕见变体 c.A1196G [p.D399G] 在 12 名个体中发现）和 1 名个体中的一种 SCARB1 罕见变体。此外，所有个体都至少有一种四种常见变体（一种 CETP 和三种 LIPC 变体）。在两名个体中还发现了另外两种未知频率的新 CETP 变体。然而，鉴定出的变体与 CEC、ROS 生成或 VCAM-1 表达没有显著关联。本研究为具有极高 HDL-C 的个体中的遗传作用提供了更多的见解。
