LPL基因突变与高甘油三酯血症相关性研究进展

高甘油三酯血症是导致动脉硬化和冠心病的主要危险因素之一。近年来研究发现除了环境饮食因素外,遗传因素在高甘油三酯血症、动脉硬化和冠心病的发生过程中起重要作用。脂蛋白脂酶(LPL)作为脂质代谢的关键酶,主要催化乳糜微粒和极低密度脂蛋白中的甘油三酯水解,释放游离脂肪酸供机体利用。大量研究表明高甘油三酯血症、糖尿病和冠心病患者都存在LPL基因突变。在高甘油三酯血症患者中LPL常见的基因突变主要是Asp9Asn、Asn291Ser、Trp86Arg、Gly188Glu、Pro207Leu、Asp250Asn、Asn318Ser和Ser474X等。实验研究表明LPL发生基因突变后影响其蛋白的质量和降低脂蛋白酶活性,造成高甘油三酯血症,并由此引起动脉硬化、冠心病及胰腺炎风险增加。本文综述了LPL基因的结构、功能、酶学特性以及LPL基因突变及其在高甘油三酯血症和冠心病发病中的研究进展。

The research progress of the association between the mutations in the LPL gene and hypertriglyceridemia

Hypertriglyceridemia （HTG） is the one of risk factors for the development of atherosclerosis and coronary artery disease （CAD）. Recent studies have shown that genetic defects of genes are playing important roles in the pathogenesis of the hypertriglyceridemia, atherosclerosis and CAD in addition to the diets and environmental factors. Lipoprotein lipase （LPL） is the rate-limiting enzyme to metabolize the triglyceride （TG） in very low density lipoprotein （VLDL） and Chylomicrons （CM） to generate the free fatty acids for the human body. A large number of different mutations in the LPL gene have been found to be associated with the hypertriglyceridemia, diabetes and CAD. The common mutations of the LPL gene identified in patients with hypertriglyceridemia are Asp9Asn, Asn291Ser, Trp86Arg, Gly188Glu, Pro207Leu, Asp250Asn,Asn318Ser and Ser474X. Experimental studies have shown that the genetic defects of the LPL gene affected its mass and the enzyme activity to hydrolyze the TG and increased the risk to develop the hypertriglyceridemia, diabetes, pancreatisis and CAD. This review summarized the research progress in the structure, function, enzyme activity and the association between the mutations in the LPL gene and the hypertriglyceridemia, diabetes and CAD.