Development and the application of a comprehensive cause-analysis system for hypertriglyceridemia that is a risk factor for coronary heart disease

高甘油三酯血症是冠心病的危险因素之一，它是由循环中主要与甘油三酯分解代谢有关的脂蛋白脂酶(LPL)异常引起的。事实上，我们发现S193R/I194T复合杂合性LPL缺陷是导致LPL活性和LPL蛋白水平低的高甘油三酯血症的原因之一。然而，有一例LPL基因在活性和蛋白水平均较低的情况下并未出现异常。在这种情况下，我们在患者的血浆中发现了一种LPL酶的抑制剂。用测定血浆对LPL活性抑制作用的方法和用Western印迹法确定LPL蛋白结合的免疫球蛋白类型的方法来检测该抑制物。测定血浆对功能性LPL活性的抑制是检测LPL酶抑制剂的关键。

Hypertriglyceridemia is one of the risk factors for coronary heart disease, and it is caused by an abnormality of lipoprotein lipase(LPL) that is mainly associated with catabolism of triglyceride in the circulation. In fact, we found a compound heterozygous LPL deficiency of S193R/I194T as a cause of hypertriglyceridemia in a subject with the low level of LPL activity and LPL protein. However, there was a case whose LPL gene had no abnormality in spite of the low level of LPL both activity and protein. In this case, we found an inhibitor of LPL enzyme in the patient's plasma. Detection of the inhibitor was done by a combination of the method of measuring inhibitory effect of the plasma on LPL activity and determining a typeof the immunoglobulin binding to LPL protein by Western blot method. Measurement of the inhibition of the functional LPL activity by plasma was essential for the detection of inhibitors of LPL enzyme.