1997 Fiscal Year Final Research Report Summary
Apolipoprotein E variants associated with lipoprotein glomerulopathy
| Project/Area Number |
08671195
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
内分泌・代謝学
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| Research Institution | Fukuoka University |
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Principal Investigator |
SASAKI Jun Fukuoka University, School of Medicine, Associate Professor, 医学部, 助教授 (90122697)
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| Co-Investigator(Kenkyū-buntansha) |
MATSUNAGA Akira Fukuoka University, School of Medicine, Lecturer, 医学部, 講師 (60221587)
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| Project Period (FY) |
1996 – 1997
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| Keywords | apolipoprotein E / apo E / mutation / recombinant / expression / lipoprotein glomerulopathy / type III hyperlipidemia |
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| Research Abstract |
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.
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