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Etiological significance of apolipoprotein E mutations in lipoprotein glomerulopathy
Takao Saito1, Yasushi Ishigaki, Shinichi Oikawa
1Department of Internal Medicine, Fukuoka University School of Medicine, Japan.
Insights
Lipoprotein glomerulopathy (LPG) is linked to a specific apolipoprotein E (apoE) mutation, apoE-Sendai. This genetic factor, alongside hyperlipidemia, contributes to kidney damage in LPG patients.
Area of Science:
- Nephrology
- Genetics
- Biochemistry
Background:
- Lipoprotein glomerulopathy (LPG) is a renal disease featuring lipoprotein thrombi in glomerular capillaries.
- LPG is associated with abnormal lipoprotein profiles and apolipoprotein E (apoE) mutations.
Purpose of the Study:
- To investigate the etiological role of the apoE-Sendai mutation in LPG.
- To establish an experimental model for LPG.
Main Methods:
- Identified apoE-Sendai mutation (R145P) in Japanese LPG patients.
- Created an LPG animal model by transducing apoE-Sendai into apoE knockout mice using an adenovirus vector.
Main Results:
- The apoE-Sendai mutation is frequent in Japanese LPG patients.
- The experimental model demonstrated LPG characteristics.
Conclusions:
- Glomerular lesions in LPG result from hyperlipidemia and in situ interactions between mutant apoE-lipoproteins and the glomerulus.
- Discusses clinical features of LPG and the link to apoE mutations.
Abstract:
Lipoprotein glomerulopathy (LPG) is a newly recognized renal disease characterized by thrombus-like lipoproteins in the glomerular capillaries and abnormal lipoprotein profiles similar to those in type III hyperlipoproteinemia. Recently, these conditions have been shown to be associated with some apolipoprotein E (apoE) mutations. We found an apoE mutation (designated apoE-Sendai) that substitutes arginine 145 with proline. This mutation occurs most frequently in Japanese patients with LPG. To elucidate the etiological role of this mutation in the apoE gene, we established an experimental model for LPG by transducing apoE-Sendai in apoE knockout mice with the use of an adenovirus vector. Based on the findings in patients with LPG and its animal model, we suggest that the glomerular lesions are not only caused by hyperlipidemia, but also by in situ interaction between lipoprotein-containing mutant apoE with the glomerulus. In this review, we outline the clinical features of LPG and discuss the relationship between apoE mutations and LPG.
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