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A novel apolipoprotein E mutation, E2 (Arg25Cys), in lipoprotein glomerulopathy
Open accessAbstract
Background Lipoprotein glomerulopathy (LPG) is characterized by intraglomerular lipoprotein thrombosis and high plasma concentrations of apolipoprotein (apo) E. An apo E variant, apo E2 (Arg145Pro) Sendai, was recently identified in three patients with LPG. We detected a novel point mutation in the apo E gene in a patient with LPG, and we characterized the mutant apo E. Methods The propositus was a 32-year-old male patient on maintenance hemodialysis because of LPG. The mutation was detected by sequencing of genomic DNA from the patient and was confirmed by restriction fragment length polymorphism (RFLP) with Aor51HI. Recombinant apo E2 (Arg25Cys) Kyoto and normal apo E3 were expressed from COS-1 cells. Low-density lipoprotein (LDL) receptor-binding activities of the variants were determined in an in vitro competition assay. Results The propositus had the apo E phenotype E2/E4, as determined by isoelectric focusing, and the genotype epsilon3/epsilon4, as determined by RFLP with HhaI. Sequence analysis of amplified DNA showed a C to T transition, changing the codon for residue 25 from arginine to cysteine. The proband was a heterozygous carrier for apo E2 (Arg25Cys) Kyoto. A family study showed that the mother was a heterozygous carrier of apo E2 Kyoto and had dysbetalipoproteinemia, but no LPG. The pathophysiological effect of this mutation was investigated in vitro by binding studies of recombinant apo E2 Kyoto to LDL receptors on human fibroblasts. The ability of recombinan…
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In the citing paper
“Although ApoE Kyoto has reduced affinity for LDLR, it is located outside the LDLR binding area.”
From Lipoprotein glomerulopathy induced by ApoE Kyoto mutation in ApoE-deficient mice (2021) · cites this paper as [11]
In the citing paper
“The APOE mutations most frequently associated with LPG are the Sendai [6] and Kyoto [7] variants (p.Pro163Arg and p.Arg43Cys, respectively), but other variants have been reported (Table 1) [8–10].”
From Lipoprotein glomerulopathy associated with the Osaka/Kurashiki APOE variant: two cases identified in Latin America (2021) · cites this paper as [7]
In the citing paper
“Lipoprotein glomerulopathy (LPG) was initially reported in Japan [2] and later known to be associated with various heterozygous ApoE variants, e.g., ApoE Sendai [3] and ApoE Kyoto [4].”
From Membranous Nephropathy-Like Apolipoprotein E Deposition Disease with Apolipoprotein E Toyonaka (Ser197Cys) and a Homozygous Apolipoprotein E2/2 (2018) · cites this paper as [3]
In the citing paper
“Studies have shown that the mutant apoE could exhibit reduced LDLR binding ability and high endothelial affinity compared with wild-type apoE3 [28].”
From Identification of a founder haplotype of APOE Kyoto variant in lipoprotein glomerulopathy (2025) · cites this paper as [28]
In the citing paper
“To date, several apoE mutations have been reported to be related to LPG, including apoE Sendai4) and apoE Kyoto5).”
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 [5]
In the citing paper
“Another variant, APOE Kyoto (Arg25Cys), is located upstream of helix 1 of the N-terminal domain (Fig.5, Table 3)87).”
From Impact of Apolipoprotein E Variants: A Review of Naturally Occurring Variants and Clinical Features (2025) · cites this paper as [87]
In the citing paper
“As for incorrectly reported variants, APOE Ganzhou (Arg43Cys)91) is correctly described as APOE (p.Arg43Cys), which is the same variant as APOE Kyoto (Arg25Cys)87).”
From Impact of Apolipoprotein E Variants: A Review of Naturally Occurring Variants and Clinical Features (2025) · cites this paper as [87]
In the citing paper
“Although the apoE Sendai mutation has been directly linked to LPG (30)(31)(32)(33), the pathogenesis of the disease is not defi ned.”
From Macrophage-derived apoESendai suppresses atherosclerosis while causing lipoprotein glomerulopathy in hyperlipidemic mice (2014) · cites this paper as [31]
In the citing paper
“The other mutations are located outside the LDLR binding region, such as ApoE Kyoto (Arg25Cys),[16] ApoE Tsukuba (Arg114Cys),[23] ApoE Kanto (Asp151dup),[24] ApoE Las Vegas (Ala152Asp),[25] ApoE Chengdu (Leu155Pro),[26] ApoE1 (del 156-173)[27] and ApoE Osaka/Kurashiki (Arg158Pro).[28]”
From A boy and his mother with lipoprotein glomerulopathy: Two case reports and literature review (2025) · cites this paper as [16]
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Apolipoprotein E–related glomerular disorders
Saito, T., Matsunaga, A., Fukunaga, M., Nagahama, K., Hara, S., & Muso, E. (2020) · Kidney International · doi:10.1016/j.kint.2019.10.031 · Cited by 77
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Metadata
- Authors
- Matsunaga, A., Sasaki, J., Komatsu, T., Kanatsu, K., Tsuji, E., Moriyama, K., Koga, T., Arakawa, K., Oikawa, S., Saito, T., Kita, T., & Doi, T.
- Affiliations
- Fukuoka University (JP)
- Tohoku University (JP)
- Venue
- Kidney International
- Publisher
- Elsevier BV
- Published
- 1999-08
- Volume
- 56
- Issue
- 2
- Pages
- 421-427
- ISSN
- 0085-2538 (ISSN-L)
- OpenAlex
- W2055138129
- Cited by
- 91
- References
- 6
- Citations by year
- 2026: 4 · 2025: 3 · 2024: 2 · 2023: 1 · 2022: 4 · 2021: 5 · 2019: 4 · 2018: 7 · 2017: 2 · 2016: 2 · 2015: 3 · 2014: 8 · 2013: 7 · 2012: 2
- FWCI
- 2.42
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Kidney International (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Ministry of Education, Culture, Sports, Science and Technology (08671195, 08671196)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipid metabolism and disorders
- Health Sciences › Medicine › Nephrology › Renal Diseases and Glomerulopathies
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipoproteins and Cardiovascular Health
- Keywords
- lipoprotein glomerulopathy, apolipoprotein E, novel point mutation, LDL receptor binding, dysbetalipoproteinemia, hemodialysis
- MeSH terms
- Adult, Aged, Apolipoproteins E, Arginine, Cysteine, Dimyristoylphosphatidylcholine, DNA Mutational Analysis, Ethnicity, Exons, Family Health, Female, Fibroblasts, Genotype, Humans, Indicators and Reagents, Iodine Radioisotopes, Japan, Kidney Diseases, Kidney Glomerulus, Male, Middle Aged, Phenotype, Protein Binding, Receptors, LDL, Polymorphism, Restriction Fragment Length, Skin, Point Mutation, DNA Primers, Apolipoprotein E2
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