Association of a Novel 3-Amino Acid Deletion Mutation of Apolipoprotein E (Apo E Tokyo) with Lipoprotein Glomerulopathy
Abstract
Lipoprotein glomerulopathy (LPG) is a newly recognized renal disease characterized by abnormal lipoprotein deposition in the glomeruli, dysbetalipoproteinemia, and a high level of plasma apolipoprotein (apo) E. We identified a novel apo E mutation in a 56-year-old Japanese male with LPG. Although the plasma cholesterol and triglyceride levels were normal, the levels of intermediate-density lipoprotein cholesterol and apo E were elevated to 13 mg/dl (0.336 mmol/l; 4.2±2.9 mg/dl, mean ± SD, in 12 normolipidemic controls) and 9.2 mg/dl, respectively. Biochemical analysis revealed an unusual apo E phenotype (E1/3). Apo E genotyping using DNA digested by a restriction enzyme (Hha I) identified a 66-bp fragment which was not seen with any of the common alleles. Sequence analysis of the amplified genomic DNA fragments showed a 9-bp deletion in exon 4 of the apo E gene resulting in a 3-amino acid deletion (residues 141–143). This novel mutation involves the region of the apo E molecule known to be critically involved in binding to its receptor, and this may well transform the apo E molecule, an inefficient ligand, to its receptor(s). How this mutations causes glomerular damage remains to be determined.
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ApoE Toyonaka occurs in the hinge region (amino acid residues 192-215) that stabilizes the connection between the N-terminal domain having the low-density lipoprotein receptor-binding region and the C-terminal domain having lipid-binding activity.
“ApoE Toyonaka occurs in the hinge region (amino acid residues 192–215) that stabilizes the connection between the N-terminal domain having low-density lipoprotein receptor-binding region and the C-terminal domain having lipids-binding activity [13].”
From Membranous Nephropathy-Like Apolipoprotein E Deposition Disease with Apolipoprotein E Toyonaka (Ser197Cys) and a Homozygous Apolipoprotein E2/2 (2018) · cites this paper as [13]
Normolipidemic or mildly hyperlipidemic cases of LPG have been reported, regardless of whether the apoE mutations are located within or distant from the LDL receptor-binding area.
“However, normolipidemic or mildly hyperlipidemic cases of LPG have also been reported, regardless of whether the apoE mutations are located within or distant from the LDL receptor-binding area17–19).”
From The Novel Apolipoprotein E Mutation ApoE Chengdu (c.518T＞C, p.L173P) in a Chinese Patient with Lipoprotein Glomerulopathy (2018) · cites this paper as [18]
In LPG, apolipoprotein E variants having 3 amino acid deletions were reported independently as apoE Tokyo (del 141-143) and apoE Maebashi (del 142-144).
“In LPG, apoE variants having 3 amino acid deletions were reported independently as apoE Tokyo (del 141-143) 10) and apoE Maebashi (del 142-144) 11) .”
From Significance of a Novel Apolipoprotein E Variant, ApoE Osaka/Kurashiki, in Lipoprotein Glomerulopathy (2011) · cites this paper as [10]
The APOE Tokyo/Maebashi mutation is found at the LDL receptor binding site of apoE.
“The APOE Tokyo/Maebashi mutation is found at the LDL receptor binding site of apoE,13 which is where most mutations associated with LPG occur.35”
From Lipoprotein Glomerulopathy, First Case Report from Canada (2022) · cites this paper as [35]
The ApoE variant found in the boy and his mother is the same as ApoE Tokyo/Maebashi.
“which was same variant as ApoE Tokyo/Maebashi.”
From A boy and his mother with lipoprotein glomerulopathy: Two case reports and literature review (2025) · cites this paper as [17]
Most of the ApoE mutations in LPG are located at the LDLR binding site and its surrounding region, particularly the HSPG binding domain.
“Most of the mutations are located at the LDLR binding site and its surrounding region, particularly the HSPG binding domain, such as ApoE Tokyo (del 141-143),[17] ApoE Maebashi (del 142-144),[18]”
From A boy and his mother with lipoprotein glomerulopathy: Two case reports and literature review (2025) · cites this paper as [17]
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A boy and his mother with lipoprotein glomerulopathy: Two case reports and literature review
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- Authors
- Konishi, K., Saruta, T., Kuramochi, S., Oikawa, S., Saito, T., Han, H., Matsunaga, A., & Sasaki, J.
- Affiliations
- Keio University (JP)
- Tohoku University (JP)
- Fukuoka University (JP)
- Venue
- Nephron
- Publisher
- S. Karger AG
- Published
- 1999
- Volume
- 83
- Issue
- 3
- Pages
- 214-218
- ISSN
- 1660-8151 (ISSN-L)
- 2235-3186
- OpenAlex
- W2032257463
- Cited by
- 54
- References
- 3
- Citations by year
- 2025: 2 · 2024: 1 · 2022: 3 · 2021: 2 · 2019: 3 · 2018: 3 · 2016: 1 · 2015: 2 · 2014: 3 · 2013: 5 · 2012: 1
- FWCI
- 2.80
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Nephron journals/Nephron journals (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Nephrology › Renal Diseases and Glomerulopathies
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipid metabolism and disorders
- Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
- Keywords
- apolipoprotein E, lipoprotein glomerulopathy, intermediate-density lipoprotein cholesterol, dysbetalipoproteinemia, kidney disease
- MeSH terms
- Apolipoproteins E, Base Sequence, Biopsy, Capillaries, DNA Mutational Analysis, Humans, Kidney Diseases, Kidney Glomerulus, Cholesterol, HDL, Cholesterol, LDL, Male, Middle Aged, Polymorphism, Restriction Fragment Length, Thrombosis, Tokyo, Cholesterol, VLDL, Sequence Deletion
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