Apolipoprotein E Sendai (arginine 145-->proline): a new variant associated with lipoprotein glomerulopathy.
Abstract
Lipoprotein glomerulopathy (LPG) is a novel disease characterized by proteinuria, lipoprotein thrombi in the glomeruli, and increased concentration of plasma apolipoprotein (apo) E. It is believed that a genetic disorder of apo E may be present and associated with the disease. Three patients with LPG were examined in this study. The patients' DNA sequences were analyzed, and a nucleotide G to C point mutation in exon 4 of the apo E gene was confirmed in each patient. This missense mutation denotes amino acid substitution of the proline residue for arginine residue at position 145 of apo E. This variant (apo E Sendai) may cause a marked molecular conformational change of the apo E. These findings suggest that a novel variant is etiologically related to LPG.
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The APOE mutations most frequently associated with LPG are the Sendai and Kyoto variants.
“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 [6]
Lipoprotein glomerulopathy (LPG) is an inherited glomerular disease caused by mutations in the APOE gene.
“Lipoprotein glomerulopathy (LPG) is an inherited glomerular disease caused by mutations in the APOE gene, usually with clinical manifestations of dysregulated lipid metabolism, proteinuria, and renal insufficiency.”
From A case report of youth-onset lipoprotein glomerulopathy with APOE Chicago mutation (2024) · cites this paper as [2]
Oikawa et al. discovered the first LPG pathogenic gene in 1997, a missense mutation in exon 4 of APOE causing the 145th amino acid arginine in the mature ApoE protein to be replaced by proline (APOE Sendai, Arg145Pro).
“Oikawa et al. later discovered the first LPG pathogenic gene in 1997, which was a missense mutation in the exon 4 of APOE, causing the 145th amino acid arginine in the mature ApoE protein to be replaced by proline. This mutation was named APOE Sendai (Arg145Pro) [2].”
From A case report of youth-onset lipoprotein glomerulopathy with APOE Chicago mutation (2024) · cites this paper as [2]
More than 15 APOE mutations, or eighteen APOE variants, have been associated with LPG.
“More than 15 APOE mutations have been associated with LPG”
From Identification of a founder haplotype of <i>APOE Kyoto</i> variant in lipoprotein glomerulopathy (2025) · cites this paper as [15]
Several apoE mutations have been reported to be related to LPG, including apoE Sendai and apoE Kyoto.
“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 [4]
The substitution of proline has been reported in 5/12 variants in the LDL receptor-binding hotspot region, including apoE Sendai, apoE Chicago, apoE Guangzhou, apoE Osaka/Kurashiki, and apoE Chengdu.
“Interestingly, the substitution of proline has been reported in 5/12 variants in this hotspot region, including apoE Sendai (p.R163P)4), apoE Chicago (p.R165P)11), apoE Guangzhou (p.R168P)12), apoE Osaka/Kurashiki (p.R176P)13, 14), and apoE Chengdu (p.L173P).”
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 [4]
The first APOE variant associated with LPG was reported in Japan and is known as APOE Sendai (Arg145Pro).
“The first APOE variant associated with LPG was reported in Japan and is known as APOE Sendai (Arg145Pro)72).”
From Impact of Apolipoprotein E Variants: A Review of Naturally Occurring Variants and Clinical Features (2025) · cites this paper as [72]
Although the apoE Sendai mutation has been directly linked to LPG, the pathogenesis of the disease is not defined.
“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 [32]
Several very rare apoE mutants are associated with a progressive glomerular disease, termed LPG, with the most common being apoE Sendai.
“Several very rare apoE mutants are associated with a progressive glomerular disease, termed LPG ( 22 ), with the most common being apoE Sendai ( 32 ).”
From Macrophage-derived apoESendai suppresses atherosclerosis while causing lipoprotein glomerulopathy in hyperlipidemic mice (2014) · cites this paper as [32]
Proline is commonly found as the first residue of the alpha helix or in turns in an amino acid arrangement.
“and is commonly found as the first residue of the alpha helix or in turns in an amino acid arrangement 1, 4)”
From Significance of a Novel Apolipoprotein E Variant, ApoE Osaka/Kurashiki, in Lipoprotein Glomerulopathy (2011) · cites this paper as [4]
ApoE Sendai comprises the majority of apolipoprotein E variants related to LPG.
“which comprises the majority of apoE variants related to LPG.”
From Significance of a Novel Apolipoprotein E Variant, ApoE Osaka/Kurashiki, in Lipoprotein Glomerulopathy (2011) · cites this paper as [4]
The substitution of proline for arginine was the first apolipoprotein E mutation in LPG, called apoE Sendai (Arg145Pro).
“the substitution of proline for arginine was the first apoE mutation in LPG, called apoE Sendai (Arg145Pro) 4)”
From Significance of a Novel Apolipoprotein E Variant, ApoE Osaka/Kurashiki, in Lipoprotein Glomerulopathy (2011) · cites this paper as [4]
Thirteen different apolipoprotein E variants have been detected in lipoprotein glomerulopathy cases since the discovery of apoE Sendai (Arg145Pro) in 1997.
“Thirteen different apoE variants were detected in LPG cases since we discovered apoE Sendai (Arg145Pro) in 1997 4) .”
From Significance of a Novel Apolipoprotein E Variant, ApoE Osaka/Kurashiki, in Lipoprotein Glomerulopathy (2011) · cites this paper as [4]
Proline acts as a structural disrupter in the middle of the alpha helix.
“Proline acts as a structural disrupter in the middle of the alpha helix”
From Significance of a Novel Apolipoprotein E Variant, ApoE Osaka/Kurashiki, in Lipoprotein Glomerulopathy (2011) · cites this paper as [4]
ApoE-Sendai corresponds to apoE phenotype E2 on IEF.
“Although apoE-Chicago [7] and apoE-Sendai [2] are the representative mutations in LPG indicating phenotype E2 on IEF”
From A case of lipoprotein glomerulopathy with a rare apolipoprotein E isoform combined with neurofibromatosis type I (2018) · cites this paper as [2]
ApoE-Sendai is one of the most frequent apoE variants in LPG patients.
“which is one of the most frequent apoE variants in LPG patients”
From A case of lipoprotein glomerulopathy with a rare apolipoprotein E isoform combined with neurofibromatosis type I (2018) · cites this paper as [2]
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- Authors
- Oikawa, S., Matsunaga, A., Saito, T., Sato, H., Seki, T., Hoshi, K., Hayasaka, K., Kotake, H., Midorikawa, H., Sekikawa, A., Hara, S., Abe, K., Toyota, T., Jingami, H., Nakamura, H., & Sasaki, J.
- Affiliations
- Tohoku University (JP)
- Venue
- Journal of the American Society of Nephrology
- Published
- 1997-05
- Volume
- 8
- Issue
- 5
- Pages
- 820-823
- ISSN
- 1046-6673 (ISSN-L)
- OpenAlex
- W2141376481
- Cited by
- 103
- References
- 11
- Citations by year
- 2026: 1 · 2025: 5 · 2024: 3 · 2023: 1 · 2022: 3 · 2021: 4 · 2019: 6 · 2018: 4 · 2017: 1 · 2016: 1 · 2015: 5 · 2014: 8 · 2013: 7 · 2012: 3
- FWCI
- 4.12
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of the American Society of Nephrology (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, missense mutations, proteinuria, glomerular disease, genetic etiology
- MeSH terms
- Aged, Alleles, Apolipoproteins E, Base Sequence, DNA, Female, Genotype, Humans, Kidney Diseases, Kidney Glomerulus, Male, Middle Aged, Mutation, Phenotype, Genetic Variation
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