Miller Michael, Zhan Min
Department of Medicine, University of Maryland Hospital and Veterans Affairs Medical Center, Baltimore, Maryland, USA.
Curr Opin Cardiol. 2004 Jul;19(4):380-4. doi: 10.1097/01.hco.0000126584.12520.b5.
High-density lipoprotein cholesterol (HDL-C) has been well established as an inverse predictor of coronary heart disease (CHD), and in recent years, investigations have focused on the genetic regulation of high-density lipoprotein. Although numerous candidate genes contribute to the low HDL-C phenotype, their impact on CHD is heterogeneous, reflecting diverse gene-gene interactions and gene-environmental relationships. This review summarizes recent data involving HDL regulatory genes and their role in atherothrombosis.
The primary genetic determinants associated with relative HDL-C deficiency states are the ATP binding cassette protein, ABCA1; apolipoprotein (APO) A1; and lecithin cholesteryl acyl transferase. Other potentially important candidates invoked in low HDL-C syndromes in humans include APOC3, lipoprotein lipase, sphingomyelin phosphodiesterase 1, and glucocerebrosidase. Molecular variation in ABCAI and APOAI and, in selected cases, lecithin cholesteryl acyl transferase deficiency have been associated with increased CHD, whereas two notable variants, APOAIMilano and APOAIParis, are associated with reduced risk.
Low HDL-C syndromes have generally been correlated with an increased risk of CHD. However, single-gene abnormalities responsible for HDL-C deficiency states may have variable effects on atherothrombotic risk.
高密度脂蛋白胆固醇（HDL-C）已被确认为冠心病（CHD）的反向预测指标，近年来，研究聚焦于高密度脂蛋白的基因调控。尽管众多候选基因导致了低HDL-C表型，但其对冠心病的影响具有异质性，反映了多样的基因-基因相互作用和基因-环境关系。本综述总结了近期涉及HDL调控基因及其在动脉粥样硬化血栓形成中作用的数据。
与相对HDL-C缺乏状态相关的主要遗传决定因素是ATP结合盒蛋白ABCA1、载脂蛋白（APO）A1和卵磷脂胆固醇酰基转移酶。在人类低HDL-C综合征中涉及的其他潜在重要候选基因包括APOC3、脂蛋白脂肪酶、鞘磷脂磷酸二酯酶1和葡糖脑苷脂酶。ABCA1和APOA1的分子变异，以及在某些情况下卵磷脂胆固醇酰基转移酶缺乏与冠心病风险增加相关，而两个显著变异体APOAIMilano和APOA1Paris与风险降低相关。
低HDL-C综合征通常与冠心病风险增加相关。然而，导致HDL-C缺乏状态的单基因异常可能对动脉粥样硬化血栓形成风险产生不同影响。
