A novel apolipoprotein E mutation, ApoE Tsukuba (Arg 114 Cys), in lipoprotein glomerulopathy
Abstract
Lipoprotein glomerulopathy (LPG) is considered a type of renal lipidosis, characterized by the presence of lipoprotein thrombi in markedly dilated capillary lumina of the affected glomeruli [1]. LPG is a rare disease; approximately 65 cases have been reported to date [2]. Patients with LPG exhibit proteinuria and progressive renal dysfunction. In most of the LPG patients, levels of intermediate-density lipoproteins are elevated, resembling type III hyperlipoproteinaemia; moreover, apolipoprotein E (ApoE) levels are also elevated. Recent genetic studies have revealed that several ApoE gene mutations are associated with LPG [3]. In this study, we report a LPG patient with a novel ApoE mutation, without plasma lipid and lipoprotein abnormalities or elevated ApoE level. An 18-year-old Japanese female was first found to have proteinuria at an annual school health check. For the workup of her proteinuria, she was admitted to Tsukuba University Hospital. Her past history was unremarkable. She had no known family history of renal diseases or lipidosis, but her mother had splenomegaly of unknown origin since the previous year.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
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 [7]
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 [17]
Many cases have showed that intensive lipid-lowering treatment including fibrate for under 100 mg/dL of serum triglyceride could significantly reduce proteinuria and achieve clinical remission.
“Many cases in our previous work and others have showed that intensive lipid-lowering treatment including fibrate for under 100 mg/dL of serum triglyceride could significantly reduce proteinuria and achieve clinical remission1, 13, 17, 21–23).”
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 [17]
Normolipidemic or mildly hyperlipidemic LPG patients also benefit from fibrate treatment.
“Notably, normolipidemic or mildly hyperlipidemic LPG patients also benefit from fibrate treatment17, 22, 23).”
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 [17]
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 [17]
APOE Tsukuba (Arg114Cys) was identified as a mutation near Cys112 in helix 3.
“APOE Tsukuba (Arg114Cys) was identified as a mutation near Cys112 in helix 3 86).”
From Impact of Apolipoprotein E Variants: A Review of Naturally Occurring Variants and Clinical Features (2025) · cites this paper as [86]
Other reported ApoE mutations located outside the LDL-receptor binding site may change the spatial conformation and stability of ApoE protein.
“Other mutations locate outside of LRBS, such as ApoE5 (Glu3Lys) [20], ApoE Kyoto (Arg25Cys) [21], ApoE Tsukuba (Arg114 Cys) [22], ApoE Las Vegas (Ala152Asp) [14], ApoE1 (Del 156-173) [23], ApoE Osak/Kurashiki (Arg158 Pro) [24], ApoE Toranomon (Gln187Glu) [25], ApoE Toyonaka (Ser 197Cys) [26], and ApoE Hong Kong (Asp230Tyr) [27]. These mutations may change the spatial conformation and stability of”
From A novel apolipoprotein E mutation, ApoE Ganzhou (Arg43Cys), in a Chinese son and his father with lipoprotein glomerulopathy: two case reports (2022) · cites this paper as [22]
The other ApoE mutations are located outside the LDLR binding region, such as ApoE Kyoto (Arg25Cys), ApoE Tsukuba (Arg114Cys), ApoE Kanto (Asp151dup), ApoE Las Vegas (Ala152Asp), ApoE Chengdu (Leu155Pro), ApoE1 (del 156-173) and ApoE Osaka/Kurashiki (Arg158Pro).
“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 [23]
Cites
Apolipoprotein E: Structure-Function Relationships
Weisgraber, K. H. (1994) · Advances in Protein Chemistry · doi:10.1016/s0065-3233(08)60642-7 · Cited by 830 · see citing works
Lipoprotein Glomerulopathy: Glomerular Lipoprotein Thrombi in a Patient With Hyperlipoproteinemia
Saito, T., Sato, H., Kudo, K.-I., Oikawa, S.-I., Shibata, T., Hara, Y., Yoshinaga, K., & Sakaguchi, H. (1989) · American Journal of Kidney Diseases · doi:10.1016/s0272-6386(89)80134-9 · Cited by 148 · see citing works
Self-citationSaito, T., Sato, H., Oikawa, S., Kudo, K., Kurihara, I., Nakayama, K., Abe, K., Yoshinaga, K., & Sakaguchi, H. (1993) · American Journal of Nephrology · doi:10.1159/000168591 · Cited by 57 · see citing works
Self-citationArai, T., Yamashita, S., Yamane, M., Manabe, N., Matsuzaki, T., Kiriyama, K., Kanayama, Y., Himeno, S., & Matsuzawa, Y. (2003) · Atherosclerosis · doi:10.1016/s0021-9150(03)00194-1 · Cited by 43 · see citing works
Murano, T., Matsumura, R., Misawa, Y., Ozaki, H., Miyashita, Y., Yoshida, S., Sueioshi, M., Sugiyama, T., & Shirai, K. (2002) · Metabolism · doi:10.1053/meta.2002.29990 · Cited by 27 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
APOE gene variants in primary dyslipidemia
Khalil, Y. A., Rabès, J.-P., Boileau, C., & Varret, M. (2021) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2021.05.007 · Cited by 170 · see citing works
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 · see citing works
Self-citationTsimihodimos, V., & Elisaf, M. (2011) · Current Opinion in Lipidology · doi:10.1097/mol.0b013e328345ebb0 · Cited by 33 · see citing works
Wu, H., Yang, Y., & Hu, Z. (2018) · Journal of Atherosclerosis and Thrombosis · doi:10.5551/jat.41996 · Cited by 24 · see citing works
Katsarou, M., Stratikos, E., & Chroni, A. (2018) · Journal of Lipid Research · doi:10.1194/jlr.m088732 · Cited by 22 · see citing works
Impact of Apolipoprotein E Variants: A Review of Naturally Occurring Variants and Clinical Features
Matsunaga, A., & Saito, T. (2025) · Journal of Atherosclerosis and Thrombosis · doi:10.5551/jat.65393 · Cited by 14 · see citing works
Self-citationCommon Apolipoprotein E Gene Mutations Contribute to Lipoprotein Glomerulopathy in China
Han, J., Pan, Y., Chen, Y., Li, X., Xing, G., Shi, J., Hou, P., Zhang, H., & Wang, H. (2010) · Nephron Clinical Practice · doi:10.1159/000276578 · Cited by 13 · see citing works
Wang, R., Zhao, C., Chen, W., Liu, Z., & Xie, F. (2022) · Journal of Medical Case Reports · doi:10.1186/s13256-022-03302-0 · Cited by 5 · see citing works
Lipoprotein glomerulopathy with a novel apolipoprotein E variant, APOE Kanto (Asp 151dup)
Yokochi, A., Matsunaga, A., Kanemoto, K., Tominaga, N., Uda, S., & Saito, T. (2024) · CEN Case Reports · doi:10.1007/s13730-024-00920-z · Cited by 3 · see citing works
Self-citationA boy and his mother with lipoprotein glomerulopathy: Two case reports and literature review
Zhang, S., Fan, L., Li, Z., Liu, T., Jing, X., & Guo, Q. (2025) · Medicine · doi:10.1097/md.0000000000041628 · Cited by 2 · see citing works
Identification of a founder haplotype of <i>APOE Kyoto</i> variant in lipoprotein glomerulopathy
Wu, H., He, Z., Yang, J., Zhou, Y., Yang, Z., Hu, Z., & Yang, Y. (2025) · Clinical Kidney Journal · doi:10.1093/ckj/sfaf234
Jackson, R. J., Dierksmeier, S., Nishtar, M., Meltzer, J., Balduin, F., Beaumont, B., Fan, Z., Sergienko, E., Olson, S., Jackson, M. R., et al. (2026) · doi:10.64898/2026.06.09.730809
- Authors
- Hagiwara, M., Yamagata, K., Matsunaga, T., Arakawa, Y., Usui, J., Shimizu, Y., Aita, K., Nagata, M., Koyama, A., Zhang, B., Mastunaga, A., Saku, K., & Saito, T.
- Affiliations
- University of Tsukuba (JP)
- Corresponding author
- Hagiwara, M.
- Venue
- Nephrology Dialysis Transplantation
- Publisher
- Oxford University Press (OUP)
- Published
- 2007-08-17
- Volume
- 23
- Issue
- 1
- Pages
- 381-384
- ISSN
- 0931-0509 (ISSN-L)
- 1460-2385
- OpenAlex
- W2164888275
- Cited by
- 27
- References
- 5
- Citations by year
- 2025: 3 · 2024: 2 · 2022: 1 · 2021: 2 · 2019: 4 · 2018: 3 · 2017: 1 · 2015: 1 · 2014: 2 · 2013: 2 · 2012: 2
- FWCI
- 0.48
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Nephrology Dialysis Transplantation (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 › Nephrology › Chronic Kidney Disease and Diabetes
- Keywords
- lipoprotein glomerulopathy, apolipoprotein E, proteinuria, intermediate density lipoprotein, type III hyperlipoproteinemia, splenomegaly
- MeSH terms
- Adolescent, Apolipoproteins E, Capillaries, Female, Humans, Kidney, Kidney Diseases, Kidney Glomerulus, Lipidoses, Lipoproteins, Mutation, Thrombosis
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
