A Novel Apolipoprotein E Mutation, ApoE Osaka (Arg158 Pro), in a Dyslipidemic Patient with Lipoprotein Glomerulopathy
Open accessAbstract
Lipoprotein glomerulopathy (LPG) is a rare disease characterized by the presence of thrombuslike deposition in markedly dilated glomerular capillaries and is often accompanied by an increased serum apolipoprotein E (apoE) level. Several gene mutations of apoE have been reported to be associated with LPG. In the current study, we report an LPG patient with a novel apoE mutation, apoE Osaka. The patient was a 45-year-old man who was hospitalized due to nephrotic syndrome. Light and electron microscopic observations of renal biopsy clearly showed characteristic findings of LPG, including lamellate thrombi in the lumen of dilated glomerular capillaries. His apoE phenotype was apoE3/2 and he had mild dyslipidemia with a mid-band on polyacrylamide gel electrophoresis. It is intriguing that the serum apoE level was within normal limits. We determined the sequence of the apoE gene using direct sequencing of the polymerase chain reaction (PCR) products. ApoE gene analysis showed a nucleotide substitution of G to C at codon 158 of exon 4. This mutation denoted an amino acid substitution of arginine residue for the proline residue at position 158 of apoE. The result of PCR associated with restriction fragment length polymorphism analysis also suggested that this mutation is heterozygous. It is possible that apoE Osaka mutation causes a conformational change of apoE protein and affects the interaction between abnormal apoE-containing lipoproteins and the endothelial cells of glomerular capillaries. The precise mechanism of LPG related with apoE Osaka, however, remains to be elucidated.
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Only five cases harboring the Osaka/Kurashiki APOE variant have been described so far.
“Only five cases harboring the Osaka/Kurashaki variant have been described so far (Table 2) [8–11].”
From Lipoprotein glomerulopathy associated with the Osaka/Kurashiki APOE variant: two cases identified in Latin America (2021) · cites this paper as [8]
The Discussion reports one patient with the apoE Osaka (Arg158 Pro) variant, so this paper supports one case in the cited group. It does not state that five Osaka/Kurashiki cases had been described; that total is not established by this source. (LLM, conf=0.87)
Experimental — accuracy not yet measuredTwo independent reports in this issue describe LPG cases with the same novel apolipoprotein E variant, apoE2 (Arg158Pro).
“In this issue, cases of LPG with the same novel variant, apoE2 (Arg158Pro), are published independently”
From Significance of a Novel Apolipoprotein E Variant, ApoE Osaka/Kurashiki, in Lipoprotein Glomerulopathy (2011) · cites this paper as [5]
The Discussion (page unavailable) reports an LPG case with the novel Arg158Pro variant, which the paper names apoE Osaka. It does not document a second independent report in the same issue, and it distinguishes apoE Osaka from apoE2, which it identifies as Arg158Cys. (LLM, conf=0.86)
Experimental — accuracy not yet measuredPatients with LPG and mild hyperlipidemia have been reported clinically.
“patients with LPG and mild hyperlipidemia have been reported clinically [5, 15].”
From Lipoprotein glomerulopathy induced by ApoE Kyoto mutation in ApoE-deficient mice (2021) · cites this paper as [15]
Until now, out of 45 cases diagnosed as LPG in Japan, there is only one with APOE Tsukuba and two with APOE Osaka/Kurashiki in which the ranges of apo E are normal.
“Until now, out of 45 cases diagnosed as LPG in Japan, there is only one with APOE Tsukuba [7] and two with APOE Osaka/Kurashiki [8,9] in which the ranges of apo E are normal.”
From Lipoprotein glomerulopathy with a novel apolipoprotein E variant, APOE Kanto (Asp 151dup) (2024) · cites this paper as [8]
LPG patients with normal serum apoE levels have been reported previously, although these levels in LPG are usually two or three times higher than the normal range.
“Actually, LPG patients with normal serum apoE levels have been reported previously13, 14, 17), although these levels in LPG are usually two or three times higher than the normal range.”
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 [14]
The variants in the two reports are called apoE Osaka and apoE Kurashiki, respectively.
“and the variants are called apoE Osaka and apoE Kurashiki, respectively 5,6) .”
From Significance of a Novel Apolipoprotein E Variant, ApoE Osaka/Kurashiki, in Lipoprotein Glomerulopathy (2011) · cites this paper as [5]
The proline substitution associated with LPG is at position 158.
“the substitution of proline as-sociated with LPG was found at position 158”
From Significance of a Novel Apolipoprotein E Variant, ApoE Osaka/Kurashiki, in Lipoprotein Glomerulopathy (2011) · cites this paper as [5]
The patients in the two reports were not relatives and lived 130 km apart.
“Patients in both reports were not relatives and the distance between their homes was 130 km”
From Significance of a Novel Apolipoprotein E Variant, ApoE Osaka/Kurashiki, in Lipoprotein Glomerulopathy (2011) · cites this paper as [5]
The Introduction describes a patient from Osaka, and the Discussion describes that patient's mutation, but neither passage compares patients from two reports. Searches for relatives, family relationships, and a 130 km distance found no passage establishing either part of the claim. Page numbers were unavailable in our copy. (LLM, conf=0.75)
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A Novel Apolipoprotein E Mutation in a Boy and His Mother with Lipoprotein GlomerulopathyPreprint
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- Authors
- Mitani, A., Ishigami, M., Watase, K., Minakata, T., & Yamamura, T.
- Affiliations
- The University of Osaka (JP)
- Osaka Red Cross Hospital (JP)
- Bukkyo University (JP)
- ORCID
- Watase, Kenji
- Venue
- Journal of Atherosclerosis and Thrombosis
- Publisher
- Japan Atherosclerosis Society
- Published
- 2011
- Volume
- 18
- Issue
- 6
- Pages
- 531-535
- ISSN
- 1340-3478 (ISSN-L)
- 1880-3873
- OpenAlex
- W1988180607
- Cited by
- 24
- References
- 21
- Citations by year
- 2025: 2 · 2024: 2 · 2022: 2 · 2021: 5 · 2019: 2 · 2018: 1 · 2015: 1 · 2014: 3 · 2013: 4 · 2012: 1
- FWCI
- 2.23
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by-nc-sa
- Locations
- Journal of Atherosclerosis and Thrombosis (publishedVersion, cc-by-nc-sa)
- 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, dyslipidemia, nephrotic syndrome, amino acid substitutions, glomerular endothelial cells, novel gene mutation
- MeSH terms
- Apolipoproteins E, DNA, Exons, Genotype, Humans, Kidney Glomerulus, Lipoproteins, Male, Middle Aged, Mutation, Polymerase Chain Reaction, Amino Acid Substitution, Dyslipidemias
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