Apolipoprotein E variants associated with lipoprotein glomerulopathy

载脂蛋白 E 变异与脂蛋白肾小球病相关

• 批准号: 08671195
• 负责人: SASAKI Jun
• 金额: $ 1.22万
• 依托单位: Fukuoka University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1996
• 资助国家: 日本
• 起止时间: 1996 至 1997
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-08671195/
• 关键词: apolipoprotein E; apo E; mutation; recombinant; expression; lipoprotein glomerulopathy; type III hyperlipidemia; リポ蛋白; アポリポ蛋白; 遺伝子; 変異体

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.

载脂蛋白 (apo) E 是乳糜微粒、极低密度脂蛋白及其残余物的主要蛋白质成分。 Apo E 是乳糜微粒残余物和低密度脂蛋白受体的配体。 apo E2 (Arg158Cys) 纯合性容易发生 III 型高脂蛋白血症，从而导致过早发生冠状动脉和外周动脉粥样硬化。脂蛋白肾小球病（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 apo E 变异，即 apo E (Arg145Pro) Sendai。对 100 名无关的日本个体进行的调查并未发现 apo E (Arg145Pro) Sendai。我们还在 apo 中发现了一种新的点突变 E 基因，apoE (arg25Cys) 京都，一名 LPG 患者。该患者是一名 30 岁男性患者，因脂蛋白肾小球病而接受维持性血液透析。他的血浆载脂蛋白 E 水平为 29.6 毫克/分升。患者中发现 apo E 表型 (e2/E4) 和基因型 (e3/E4) 存在差异。功能性 通过在大肠杆菌或 COS-1 细胞中表达突变型和野生型重组 apo E cDNA 来检查突变的后果。重组apo E京都表现出LDL-受体结合强度比正常apo E3活性降低了6-7%。总之，这些数据表明apo E基因突变可能导致脂蛋白肾小球病。

项目成果

Shinichi Oikawa. et al.: "Apolipoprotein E Sendai (Arginine 145*Proline) : A New Variant Associated with Lopoprotein Glomerulopathy" Journal of American Society of Nephrology. 8. 820-823 (1997)

及川慎一.