遗传和观察性证据：胆固醇流出率与静态高密度脂蛋白浓度指标在冠心病风险评估中无独立作用。
Genetic and observational evidence: No independent role for cholesterol efflux over static high-density lipoprotein concentration measures in coronary heart disease risk assessment.
机构信息
Computational Medicine, Faculty of Medicine, University of Oulu, Oulu, Finland.
Center for Life Course Health Research, Faculty of Medicine, University of Oulu, Oulu, Finland.
出版信息
J Intern Med. 2022 Jul;292(1):146-153. doi: 10.1111/joim.13479. Epub 2022 Mar 22.
BACKGROUND
Observational findings for high-density lipoprotein (HDL)-mediated cholesterol efflux capacity (HDL-CEC) and coronary heart disease (CHD) appear inconsistent, and knowledge of the genetic architecture of HDL-CEC is limited.
OBJECTIVES
A large-scale observational study on the associations of HDL-CEC and other HDL-related measures with CHD and the largest genome-wide association study (GWAS) of HDL-CEC.
PARTICIPANTS/METHODS: Six independent cohorts were included with follow-up data for 14,438 participants to investigate the associations of HDL-related measures with incident CHD (1,570 events). The GWAS of HDL-CEC was carried out in 20,372 participants.
RESULTS
HDL-CEC did not associate with CHD when adjusted for traditional risk factors and HDL cholesterol (HDL-C). In contradiction, almost all HDL-related concentration measures associated consistently with CHD after corresponding adjustments. There were no genetic loci associated with HDL-CEC independent of HDL-C and triglycerides.
CONCLUSION
HDL-CEC is not unequivocally associated with CHD in contrast to HDL-C, apolipoprotein A-I, and most of the HDL subclass particle concentrations.
背景
关于高密度脂蛋白（HDL）介导的胆固醇流出能力（HDL-CEC）与冠心病（CHD）的观察结果似乎不一致，且对 HDL-CEC 的遗传结构知之甚少。
目的
本研究开展了一项针对 HDL-CEC 与其他 HDL 相关指标与 CHD 之间关联的大规模观察性研究，以及针对 HDL-CEC 的最大全基因组关联研究（GWAS）。
参与者/方法：纳入了 6 个独立队列，随访了 14438 名参与者，以调查 HDL 相关指标与冠心病（1570 例事件）的发病风险之间的关联。在 20372 名参与者中进行了 HDL-CEC 的 GWAS。
结果
在调整传统危险因素和高密度脂蛋白胆固醇（HDL-C）后，HDL-CEC 与 CHD 无关。相反，在进行相应调整后，几乎所有与 HDL 相关的浓度指标都与 CHD 一致相关。没有与 HDL-C 和甘油三酯无关的独立于 HDL-CEC 的遗传位点。
结论
与 HDL-C、载脂蛋白 A-I 和大多数 HDL 亚类颗粒浓度不同，HDL-CEC 与 CHD 没有明确关联。
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