Apolipoprotein E variants associated with lipoprotein glomerulopathy

载脂蛋白(Apo)E是极低密度脂蛋白乳糜粒及其残留物的主要蛋白质成分。载脂蛋白E是乳糜粒残留物和低密度脂蛋白受体的配体。Apo E2纯合子(Arg158Cys)--易患III型高脂蛋白血症，导致过早冠状动脉和外周动脉粥样硬化。脂蛋白肾小球病变(LPG9)是一种以肾小球内脂蛋白血栓和III型高脂蛋白血症为特征的疾病。我们在10名独立的LPG患者中发现了载脂蛋白E(Arg145Pro)仙台，对100名无关日本人的调查没有发现载脂蛋白E(Arg145Pro)仙台。我们还在一例LPG患者中发现了一个新的apoE基因点突变，apoE(Arg25Cys)YYOKY。先证者是一名30岁的男性患者，因脂蛋白肾小球疾病而进行维持性血液透析。他血浆载脂蛋白E水平为29.6 mg/dl。患者的载脂蛋白E表型(e2/E4)和基因分型(e3/E4)存在差异。通过在大肠杆菌或COS-1细胞中表达突变的和野生型的apoE cDNA来检测突变的功能后果。重组载脂蛋白E京都蛋白显示低密度脂蛋白受体结合活性从正常载脂蛋白E3的6-7%降低。综上所述，这些数据提示载脂蛋白E基因突变可能导致脂蛋白肾小球病变。

Apolipoprotein (apo) E is a major protein constituent of chylomicrons, very low density lipoprotein, and their remnants. Apo E is a ligand for the chylomicron remnant and low density lipoprotein receptors. Homozygosity for apo E2 (Arg158Cys)-predisposes to the development of type III hyperlipoproteinemia which developed premature coronary and peripheral atherosclerosis. Lipoprotein glomerulopathy (LPG9 is a disease characterized by intraglomerular lipoprotein thrombi and type III hyperlipoproteinemia. We identified apo E variant, apo E (Arg145Pro) Sendai in ten independent patients with LPG.A survey of 100 unrelated Japanese individuals did not identify an apo E (Arg145Pro) Sendai. We also found a novel point mutation in apo E gene, apoE (arg25Cys) Kyoto in a patient with LPG.The propositus was a 30-year-old male patient on maintenance hemodialysis due to lipoprotein glomerulopathy. His plasma apo E level was 29.6mg/dl. Disdcrepancy in apo E phenotype (e2/E4) and genotype (e3/E4) was seen in the patient. Functional consequences of the mutation were examined by expressing the mutated and wild-type recombinant apo E cDNAs in E.coli or COS-1 cells. Recombinant apo E Kyoto showed a reduction in LDL-receptor binding renging from 6-7% of activity of normal apo E3. In conclusion.these data suggest that the mutation in the apo E gene may cause lipoprotein glomerulopathy.