Department of Vascular Medicine, Academic Medical Center, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands.
Curr Atheroscler Rep. 2013 Jun;15(6):326. doi: 10.1007/s11883-013-0326-8.
Prospective epidemiological studies have consistently reported an inverse association between HDL cholesterol (HDL-C) levels and the risk of cardiovascular disease (CVD). However, large intervention trials on HDL-C-increasing drugs and recent Mendelian randomization studies have questioned a causal relationship between HDL-C and atherosclerosis. HDL-C levels have been shown to be highly heritable, and the combination of HDL-C-associated SNPs in recent large-scale genome-wide association studies (GWAS) only explains a small proportion of this heritability. As a large part of our current understanding of HDL metabolism comes from genetic studies, further insights in this research field may aid us in elucidating HDL functionality in relation to CVD risk. In this review we focus on the question of whether genetically defined HDL-C levels are associated with risk of atherosclerosis. We also discuss the latest insights for HDL-C-associated genes and recent GWAS data.
前瞻性流行病学研究一致报告，高密度脂蛋白胆固醇（HDL-C）水平与心血管疾病（CVD）风险呈负相关。然而，针对升高 HDL-C 的药物的大型干预试验和最近的孟德尔随机化研究对 HDL-C 与动脉粥样硬化之间的因果关系提出了质疑。HDL-C 水平具有高度遗传性，最近大规模全基因组关联研究（GWAS）中与 HDL-C 相关的 SNP 组合仅能解释一小部分遗传率。由于我们目前对 HDL 代谢的认识很大程度上来自遗传研究，因此在该研究领域的进一步深入研究可能有助于我们阐明与 CVD 风险相关的 HDL 功能。在这篇综述中，我们重点探讨了遗传定义的 HDL-C 水平是否与动脉粥样硬化风险相关的问题。我们还讨论了与 HDL-C 相关的基因的最新研究进展和最近的 GWAS 数据。
