Apolipoprotein E variants associated with lipoprotein glomerulopathy

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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.