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Cited by 2Renal Diseases and GlomerulopathiesLipid metabolism and disordersChronic Kidney Disease and Diabetes

The DOI matches its Crossref record; 21 of the 21 references it cites were found in a registry or an index; 12 of the 35 sources its claims cite were checked for support.

A case report of youth-onset lipoprotein glomerulopathy with APOE Chicago mutation

Open access
Liu, Yuhao, Cheng, Yaqi, Wen, Yubing, Li, Chao, Chen, Gang, Li, Mingxi·2024·BMC Nephrology
DOI 10.1186/s12882-024-03515-zPMC PMC10918868
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Abstract

Background: This article reports an extremely rare case of lipoprotein glomerulopathy (LPG) with apolipoprotein E gene (APOE) Chicago mutation in a young Chinese male. Only five cases or families with APOE Chicago mutations have been reported in the literature. Case presentation: The young male patient is manifested with nephrotic syndrome, accompanied by hyperlipidemia with a preferable increase in triglycerides and elevated ApoE level. Renal biopsy of the patient showed highly dilated glomerular capillaries filled with vacuolar lipids, segmentally fused podocyte foot processes, vacuolar degeneration of renal tubular epithelial cells and absence of electron-dense material, which indicates the diagnosis of LPG. Whole-exome gene sequencing identified the heterozygous mutation of NM_000041.4:c.494G > C (p.Arg165Pro), which is in the exon 4 of the APOE gene and also known as APOE Chicago mutation, a rare mutation of LPG. Further family pedigree gene analysis clarified that the mutation was inherited from the patient’s mother, who does not have high ApoE levels or renal manifestations. This is also consistent with the incomplete penetrance of APOE gene mutations in LPG. Under lipid-lowering treatments, including a low-fat diet and fenofibrate, the patient’s urinary protein was partially controlled, and the albumin level was recovered. Conclusion: Patients with nephrotic syndrome and elevated ApoE levels should be prompted into renal biopsy to avoid delay of appropriate treatment and unnecessary use of glucocorticoids. This case of LPG was diagnosed by renal biopsy and further verified with genetic sequencing. The timely diagnosis and treatment improved the patient’s symptoms. This case is one of only six reported LPG cases or families with APOE Chicago mutation in the world.

Overview

AI snapshot

Written from the paper’s full text.

TL;DR

This case report describes a 26-year-old Chinese male with youth-onset lipoprotein glomerulopathy (LPG) caused by the rare heterozygous APOE Chicago mutation (NM_000041.4:c.494G>C, p.Arg165Pro), inherited from his mother who had no renal manifestations. Renal biopsy and genetic sequencing supported the diagnosis, and lipid-lowering treatment with fenofibrate plus a low-fat diet partially controlled proteinuria and improved albumin.

Key findings

  • The patient presented with nephrotic syndrome and hyperlipidemia: initial 24-hour urine protein 3.84 g, albumin 29.9 g/L, creatinine 83 µmol/L, total cholesterol 6.83 mmol/L, triglycerides 6.37 mmol/L; later 24-hour urine protein rose to 7.24 g, and ApoE was elevated at 5.97 mg/dL (reference 2.7–4.9 mg/dL).
  • Renal biopsy showed enlarged glomeruli with highly dilated capillaries filled with vacuolar/laminar lipids, segmental sclerosis in 3 of 67 glomeruli, podocyte foot process fusion, tubular epithelial vacuolar degeneration, and no electron-dense material, consistent with LPG.
  • Whole-exome sequencing identified a heterozygous APOE mutation, NM_000041.4:c.494G>C (p.Arg165Pro), known as APOE Chicago; the same mutation was found in his mother, who had normal ApoE levels and preserved kidney function, consistent with incomplete penetrance.
  • After treatment with fenofibrate and a low-fat diet, follow-up showed partial improvement: albumin 45 g/L, creatinine 77 µmol/L, 24-hour urine protein 3.09 g, total cholesterol 4.12 mmol/L, and triglycerides 2.06 mmol/L. The paper states this is one of only six reported LPG cases or families with APOE Chicago mutation worldwide.

Methods

  • Single case report of a young Chinese male with nephrotic syndrome and suspected LPG.
  • Diagnostic workup included renal biopsy with light microscopy, immunofluorescence, and electron microscopy, plus whole-exome sequencing of the patient and his parents.
  • The APOE variant was classified using ACMG guidelines as a suspected pathogenic variant (PS4_Supporting + PM1 + PM2 + PP4), and prior APOE Chicago cases were summarized in a literature table.

Limitations

  • The paper states that studies are needed to specify the influences of various APOE mutations in LPG and that functional verification is required to further improve understanding of this rare disease.
  • The text makes evident that this is a single case report, so findings are not generalizable and no controlled comparison of treatments is provided.
  • The text does not report the duration of follow-up or long-term renal outcomes after the partial response to fenofibrate and diet.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.1186/s12882-024-03515-z

Cites

21 of 21 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Verification

Claims the paper makes

12 of 35 cited sources checked · 5 supported · 0 flagged · accuracy not yet measured

  • Findingown data

    Whole-exome sequencing identified a heterozygous mutation in the APOE gene NM_000041.4:c.494G>C (p.Arg165Pro).

    “whole exon sequncing was applied and revealed a heterozygous mutation of the patient in APOE gene NM_000041.4:c.494G > C(p.Arg165Pro).”
    Quote in the paperSubstantial claim
  • Findingown data

    The patient was diagnosed with nephrotic syndrome.

    “Nephrotic syndrome was diagnosed, and screening for hepatitis B, antinuclear antibody profile, and anti-phospholipase A2 receptor antibody were all negative.”
    Quote in the paperNot a substantial claim
  • Findingown data

    Renal biopsy showed segmental sclerosis in 3 out of 67 glomeruli.

    “renal biopsy was conducted and showed segmental sclerosis in 3 out of 67 glomeruli in the light microscopy.”
    Quote in the paperNot a substantial claim
  • Findingown data

    The APOE mutation NM_000041.4:c.494G>C (p.Arg165Pro) was inherited from the patient's mother.

    “Further family pedigree gene analysis clarified that the mutation was inherited from the patient’s mother, who does not have high ApoE levels or renal manifestations.”
    • Also stated in: § Case presentation · plain
      “clarifying the inheritance of the pathogenic mutation.”
    Quote in the paperSubstantial claim
  • Findingown data

    The patient's treatment with fenofibrate and irbesartan resulted in partial alleviation with Alb 45 g/L, Cr 77 μmol/L, 24hUP 3.09 g, TC 4.12 mmol/L, and TG 2.06 mmol/L.

    “Subsequent follow up revealed partial alleviation with Alb 45 g/L, Cr 77µmol/L, 24hUP 3.09 g, TC 4.12mmol/L and TG 2.06mmol/L, further support the LPG diagnosis.”
    Quote in the paperSubstantial claim
  • Probably not a substantial claim. 14
  • It may state two separate claims as one. 25
  • The quote only partly states this claim. 1

  • Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.

    Premisecitation

    17 APOE gene mutations have been related to LPG and more than 200 cases have been reported worldwide up to date.

    “With a deepened understanding of LPG and widespread application of gene sequencing, 17 APOE gene mutations have been related to LPG and more than 200 cases have been reported worldwide up to date.”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [3] Li MS, Li Y, Liu Y, Zhou XJ, Zhang H. An Updated Review and Meta Analysis of Lipoprotein Glomerulopathy. Front Med (Lausanne). 2022;9:905007. source

  • Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.

    Premisecitation

    Chinese LPG patients have the highest incidence of APOE Kyoto (Arg25Cys) mutations, while Japanese LPG patients mainly have APOE Sendai (Arg145Pro) mutations.

    “Among them, Chinese LPG patients have the highest incidence of APOE Kyoto (Arg25Cys) mutations, while Japanese LPG patients mainly have APOE Sendai (Arg145Pro) mutations [3, 4].”
    Quote in the paperNot a substantial claim1 of 2 sources checked
    • cites [3] Li MS, Li Y, Liu Y, Zhou XJ, Zhang H. An Updated Review and Meta Analysis of Lipoprotein Glomerulopathy. Front Med (Lausanne). 2022;9:905007. source
    • cites [4] Saito T, Matsunaga A, Ito K, Nakashima H. Topics in lipoprotein glomerulopathy: an overview. Clin Exp Nephrol. 2014;18(2):214–7. source

  • It may state two separate claims as one.

    Premisecitation

    The APOE mutation NM_000041.4:c.494G>C (p.Arg165Pro) is in exon 4 of APOE and is known as APOE Chicago mutation.

    “which is in the exon 4 of the APOE gene and also known as APOE Chicago mutation, a rare mutation of LPG.”
    • Also stated in: § Discussion and conclusion · plain
      “Further whole exon sequencing of the patient identified the pathogenic APOE Chicago (Arg147Pro) mutation, which has only been reported in five patients/families so far and their characteristics are summarized in Table 1.”
    Quote in the paperSubstantial claim1 of 3 sources checked
    • cites [5] Watanabe Y, Ozaki I, Yoshida F, Fukatsu A, Itoh Y, Matsuo S, et al. A case of nephrotic syndrome with glomerular lipoprotein deposition with capillary ballooning and mesangiolysis. Nephron. 1989;51(2):265–70. source
    • cites [7] Sam R, Wu H, Yue L, Mazzone T, Schwartz MM, Arruda JA, et al. Lipoprotein glomerulopathy: a new apolipoprotein E mutation with enhanced glomerular binding. Am J Kidney Dis. 2006;47(3):539–48. source
    • cites [9] Yang M, Weng Q, Pan X, Hussain HMJ, Yu S, Xu J, et al. Clinical and genetic analysis of lipoprotein glomerulopathy patients caused by APOE mutations. Mol Genet Genomic Med. 2020;8(8):e1281. source

      The Results (Genotyping; page unavailable) identify c.494G>C (p.R165P) as the APOE-Chicago mutation in a patient with lipoprotein glomerulopathy. The Methods (Sanger sequencing; page unavailable) say the authors sequenced APOE’s four exons using reference sequence NM_000041.4, but our copy does not specify that this mutation is in exon 4. (LLM, conf=0.88)

      Experimental — accuracy not yet measured

  • It may state two separate claims as one.

    Premisecitation

    Many LPG pathogenic APOE mutations, such as APOE Kyoto (Arg25Cys), APOE Sendai (Arg145Pro), and APOE Chicago (Arg147Pro), significantly reduce the helicity of ApoE protein and increase its thermodynamic instability.

    “Studies have found that many LPG pathogenic APOE mutations, such as APOE Kyoto (Arg25Cys), APOE Sendai (Arg145Pro), and APOE Chicago (Arg147Pro), significantly reduce the helicity of ApoE protein and increase its thermodynamic instability [17, 18].”
    Quote in the paperSubstantial claim2 of 2 sources checked
    • cites [17] Georgiadou D, Stamatakis K, Efthimiadou EK, Kordas G, Gantz D, Chroni A, et al. Thermodynamic and structural destabilization of apoE3 by hereditary mutations associated with the development of lipoprotein glomerulopathy. J Lipid Res. 2013;54(1):164–76. source

      The paper reports significantly reduced helical content and thermodynamic stability for apoE Sendai (R145P) and Chicago (R147P). Its study examined those variants and Osaka/Kurashiki (R158P), not Kyoto (R25C), so it does not support the claim about Kyoto. (LLM, conf=0.90)

      Experimental — accuracy not yet measured
    • cites [18] Katsarou M, Stratikos E, Chroni A. Thermodynamic destabilization and aggregation propensity as the mechanism behind the association of apoE3 mutants and lipoprotein glomerulopathy. J Lipid Res. 2018;59(12):2339–48. source

  • Probably not a substantial claim. The paper’s conclusions may not depend on it.

    Premisecitation

    The APOE Chicago mutation has only been reported in five patients/families so far.

    “which has only been reported in five patients/families so far and their characteristics are summarized in Table 1.”
    Quote in the paperNot a substantial claim1 of 3 sources checked
    • cites [5] Watanabe Y, Ozaki I, Yoshida F, Fukatsu A, Itoh Y, Matsuo S, et al. A case of nephrotic syndrome with glomerular lipoprotein deposition with capillary ballooning and mesangiolysis. Nephron. 1989;51(2):265–70. source
    • cites [7] Sam R, Wu H, Yue L, Mazzone T, Schwartz MM, Arruda JA, et al. Lipoprotein glomerulopathy: a new apolipoprotein E mutation with enhanced glomerular binding. Am J Kidney Dis. 2006;47(3):539–48. source
    • cites [9] Yang M, Weng Q, Pan X, Hussain HMJ, Yu S, Xu J, et al. Clinical and genetic analysis of lipoprotein glomerulopathy patients caused by APOE mutations. Mol Genet Genomic Med. 2020;8(8):e1281. source

      The Discussion (page unavailable) describes APOE-Chicago in a Mexican-American patient, a Japanese patient, and, for the first time in China, a patient in this study. The Results > Genotyping section (page unavailable) identifies one Chicago patient; its count of five refers to APOE-Kyoto, not Chicago. The source supports that Chicago was rarely reported, but not the claimed count of five patients or families. (LLM, conf=0.87)

      Experimental — accuracy not yet measured

  • It may state two separate claims as one.

    Premisecitation

    Several cases are reported to have glomerular lesions called ApoE2 homozygote glomerulopathy, characterized by foam cell infiltration and different from LPG.

    “Additionally, several cases are reported to have glomerular lesions as called ApoE2 homozygote glomerulopathy, which is characterized by foam cell infiltration and different from LPG [16].”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [16] Kawanishi K, Sawada A, Ochi A, Moriyama T, Mitobe M, Mochizuki T, et al. Glomerulopathy with homozygous apolipoprotein e2: a report of three cases and review of the literature. Case Rep Nephrol Urol. 2013;3(2):128–35. source

  • It may state two separate claims as one.

    Premisecitation

    Mutated ApoE is more prone to denaturation at physiological temperature and possesses significantly higher aggregation tendency.

    “Mutated ApoE is more prone to denaturation at physiological temperature and possesses significantly higher aggregation tendency [17, 18].”
    Quote in the paperSubstantial claim2 of 2 sources checked
    • cites [17] Georgiadou D, Stamatakis K, Efthimiadou EK, Kordas G, Gantz D, Chroni A, et al. Thermodynamic and structural destabilization of apoE3 by hereditary mutations associated with the development of lipoprotein glomerulopathy. J Lipid Res. 2013;54(1):164–76. source
    • cites [18] Katsarou M, Stratikos E, Chroni A. Thermodynamic destabilization and aggregation propensity as the mechanism behind the association of apoE3 mutants and lipoprotein glomerulopathy. J Lipid Res. 2018;59(12):2339–48. source

      The ‘Aggregation propensity’ section reports that three apoE3 mutants became more aggregation-prone than WT after 24 hours at 37°C. The ‘Thermodynamic stability’ section reports reduced stability in denaturation tests, but it does not establish that the mutants denature at physiological temperature; only two of the three unfolded at a significantly lower temperature than WT. (LLM, conf=0.86)

      Experimental — accuracy not yet measured

  • It may state two separate claims as one.

    Interpretationcitation

    Mutated ApoE-containing lipoproteins have higher aggregation tendency and are prone to interact with glomerular capillary endothelial cells and deposit in the glomerulus, which together lead to LPG pathogenesis.

    “These mutated lipoproteins are with higher aggregation tendency and prone to interact with glomerular capillary endothelial cells and deposit in the glomerulus, which together lead to the pathogenesis of LPG.”
    Quote in the paperSubstantial claim2 of 3 sources checked
    • cites [17] Georgiadou D, Stamatakis K, Efthimiadou EK, Kordas G, Gantz D, Chroni A, et al. Thermodynamic and structural destabilization of apoE3 by hereditary mutations associated with the development of lipoprotein glomerulopathy. J Lipid Res. 2013;54(1):164–76. source

      The section “Mutations cause aggregation of apoE3 and structurally defective lipoprotein particles” (page unavailable) supports increased aggregation of mutant apoE-containing particles and proposes that this may contribute to kidney deposition. It does not establish an interaction with glomerular capillary endothelial cells; the paper says the mechanism of deposition is unknown and presents increased affinity for the glomerulus as a proposal, not a demonstrated cause of LPG. (LLM, conf=0.87)

      Experimental — accuracy not yet measured
    • cites [18] Katsarou M, Stratikos E, Chroni A. Thermodynamic destabilization and aggregation propensity as the mechanism behind the association of apoE3 mutants and lipoprotein glomerulopathy. J Lipid Res. 2018;59(12):2339–48. source

      The Abstract reports that LPG-associated apoE3 variants are aggregation-prone, and the Discussion proposes that mutant apoE may aggregate in glomerular capillaries and promote lipoprotein thrombi. Neither passage says that the lipoproteins interact with glomerular capillary endothelial cells. The Discussion presents the proposed deposition mechanism as a hypothesis, not an established cause of LPG. (LLM, conf=0.87)

      Experimental — accuracy not yet measured
    • cites [19] Murano T, Matsumura R, Misawa Y, Ozaki H, Miyashita Y, Yoshida S, et al. Interaction of endothelial cells and triglyceride-rich lipoproteins with apolipoprotein E (Arg–>Cys) from a patient with lipoprotein glomerulopathy. Metabolism. 2002;51(2):201–5. source

  • Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.

    Premisecitation

    Amino acids 140-150 in the N-terminal domain are LDL receptor binding sites, and amino acids 244-272 in the C-terminal domain are binding sites for lipids.

    “Amino acids 140–150 in the N-terminal domain are low-density lipoprotein (LDL) receptor binding sites, and amino acids 244–272 in the C-terminal domain are binding sites for lipids [11].”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [11] Guttman M, Prieto JH, Croy JE, Komives EA. Decoding of lipoprotein-receptor interactions: properties of ligand binding modules governing interactions with apolipoprotein E. Biochemistry. 2010;49(6):1207–16. source

      The paper’s introductory passage identifies ApoE residues 140–150 in the N-terminal domain as a critical receptor-recognition site. It also says the C-terminal domain is involved in lipid binding, but the passages do not identify residues 244–272 as the lipid-binding site (page numbers are unavailable in our copy). (LLM, conf=0.87)

      Experimental — accuracy not yet measured

  • It may state two separate claims as one.

    Findingown data

    Renal biopsy showed enlarged glomeruli and highly dilated glomerular capillaries filled with vacuolar or laminar lipids.

    “The patient’s glomeruli were enlarged, and glomerular capillaries were highly dilated filled with vacuolar or laminar lipids.”
    Quote in the paperSubstantial claim

  • It may state two separate claims as one.

    Findingown data

    Electron microscopy showed dilated glomerular capillary loop lumen filled with large amounts of lipid vacuoles, segmentally fused podocyte foot processes, and no electron dense material.

    “Electron microscopy: dilated glomerular capillary loop lumen was filled with large amounts of lipid vacuoles, podocyte foot process was segmentally fused, and no electron dense material was found (Fig. 2).”
    Quote in the paperSubstantial claim

  • It may state two separate claims as one.

    Findingnone given

    The young Chinese male patient developed facial and lower limb edema at the age of 26, accompanied by loss of appetite, increased foam in the urine, and rapid gain of body weight.

    “The young Chinese male patient developed facial and lower limb edema at the age of 26, accompanied by loss of appetite, increased foam in the urine, and rapid gain of body weight.”
    Quote in the paperNot a substantial claim

  • It may state two separate claims as one. The quote only partly states this claim.

    Findingown data

    The patient had hyperlipidemia with elevated triglycerides and elevated ApoE level.

    “Apolipoprotein E (ApoE) level was found to be increased as 5.97 mg/dL (2.7–4.9 mg/dL), whilst Apolipoprotein A1 and Apolipoprotein B levels were within the normal range.”
    • Also stated in: § Case presentation · plain
      “total cholesterol (TC) 6.83mmol/L, triglyceride (TG) 6.37mmol/L.”
    Quote in the paperNot a substantial claim

  • It may state two separate claims as one.

    Findingown data

    The patient's mother has normal ApoE levels and preserved kidney function with no proteinuria and hematuria.

    “his mother exhibited normal ApoE levels and preserved kidney function with no proteinuria and hematuria.”
    Quote in the paperSubstantial claim

  • It may state two separate claims as one.

    Findingown data

    Under lipid-lowering treatments including a low-fat diet and fenofibrate, the patient's urinary protein was partially controlled and albumin level recovered.

    “Under lipid-lowering treatments, including a low-fat diet and fenofibrate, the patient’s urinary protein was partially controlled, and the albumin level was recovered.”
    • Also stated in: § Case presentation · plain
      “Subsequent follow up revealed partial alleviation with Alb 45 g/L, Cr 77µmol/L, 24hUP 3.09 g, TC 4.12mmol/L and TG 2.06mmol/L, further support the LPG diagnosis.”
    Quote in the paperNot a substantial claim

  • It may state two separate claims as one.

    Findingown data

    The patient's father has wild-type APOE, while the patient's mother carries the same heterozygous mutation NM_000041.4:c.494G>C (p.Arg165Pro).

    “The patient’s father has wild-type APOE, while the patient’s mother carries the same heterozygous mutation in NM_000041.4:c.494G > C(p.Arg165Pro), clarifying the inheritance of the pathogenic mutation.”
    Quote in the paperSubstantial claim

  • It may state two separate claims as one.

    Findingown data

    This case of LPG was diagnosed by renal biopsy and further verified with genetic sequencing.

    “This case of LPG was diagnosed by renal biopsy and further verified with genetic sequencing.”
    Quote in the paperSubstantial claim

  • It may state two separate claims as one.

    Findingreasoning

    The patient's APOE genotype was E3/E3 or E3/E4.

    “Accordingly, genotype E3/E3 or E3/E4 are identified in LPG as in our patient.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim. The paper’s conclusions may not depend on it.

    Premisecitation

    The first 2 cases of LPG were reported by Saito et al. in the same family in 1989.

    “The first 2 cases of LPG were reported by Japanese scholar Saito et al. in the same family in 1989 [1].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [1] Saito T, Sato H, Kudo K, Oikawa S, Shibata T, Hara Y, et al. Lipoprotein glomerulopathy: glomerular lipoprotein thrombi in a patient with hyperlipoproteinemia. Am J Kidney Dis. 1989;13(2):148–53. source

  • Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.

    Premisecitation

    Diagnosis of LPG relies primarily on renal pathology, with typical lipoprotein thrombosis within dilated glomerular capillary loops.

    “Diagnosis of LPG relies primarily on renal pathology, with typical lipoprotein thrombosis within dilated glomerular capillary loops.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [1] Saito T, Sato H, Kudo K, Oikawa S, Shibata T, Hara Y, et al. Lipoprotein glomerulopathy: glomerular lipoprotein thrombi in a patient with hyperlipoproteinemia. Am J Kidney Dis. 1989;13(2):148–53. source

  • Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.

    Premisecitation

    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].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [2] Oikawa S, Matsunaga A, Saito T, Sato H, Seki T, Hoshi K, et al. Apolipoprotein E Sendai (arginine 145–>proline): a new variant associated with lipoprotein glomerulopathy. J Am Soc Nephrol. 1997;8(5):820–3. source

  • It may state two separate claims as one.

    Premisecitation

    Mutated ApoE exhibits increased affinity to endothelial cells, as found in APOE Kyoto (Arg25Cys) and APOE Chicago (Arg147Pro), which helps drive lipoproteins to deposit primarily in the capillary lumina of glomerulus and eventually cause LPG.

    “Moreover, mutated ApoE also exhibits increased affinity to endothelial cells, as found in APOE Kyoto (Arg25Cys) and APOE Chicago (Arg147Pro), which help drive lipoproteins to deposit primarily in the capillary lumina of glomerulus and eventually cause LPG [7, 19].”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [7] Sam R, Wu H, Yue L, Mazzone T, Schwartz MM, Arruda JA, et al. Lipoprotein glomerulopathy: a new apolipoprotein E mutation with enhanced glomerular binding. Am J Kidney Dis. 2006;47(3):539–48. source
    • cites [19] Murano T, Matsumura R, Misawa Y, Ozaki H, Miyashita Y, Yoshida S, et al. Interaction of endothelial cells and triglyceride-rich lipoproteins with apolipoprotein E (Arg–>Cys) from a patient with lipoprotein glomerulopathy. Metabolism. 2002;51(2):201–5. source

  • Probably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds.

    Interpretationnone given

    This case is one of only six reported LPG cases or families with APOE Chicago mutation in the world.

    “This case is one of only six reported LPG cases or families with APOE Chicago mutation in the world.”
    Quote in the paperNot a substantial claim

  • It may state two separate claims as one.

    Premisecitation

    These mutations mitigate the binding ability of ApoE protein to LDL receptor, resulting in elevations of ApoE in the circulation, and could be an essential mechanism in LPG development.

    “These mutations mitigate the binding ability of ApoE protein to LDL receptor, resulting in elevations of ApoE in the circulation, and could be an essential mechanism in the LPG development [12].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [12] Hoffmann MM, Scharnagl H, Panagiotou E, Banghard WT, Wieland H, März W. Diminished LDL receptor and high heparin binding of apolipoprotein E2 Sendai associated with lipoprotein glomerulopathy. J Am Soc Nephrol. 2001;12(3):524–30. source

  • Probably not a substantial claim. The paper’s conclusions may not depend on it.

    Premisecitation

    More than 95% of type III hyperlipoproteinemia individuals carry homozygous APOE2 mutation.

    “more than 95% of type III hyperlipoproteinemia individuals carry homozygous APOE2 mutation [14].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [14] Matsunaga A, Saito T. Apolipoprotein E mutations: a comparison between lipoprotein glomerulopathy and type III hyperlipoproteinemia. Clin Exp Nephrol. 2014;18(2):220–4. source

  • It may state two separate claims as one.

    Premisecitation

    Most homozygous APOE2 carriers are normolipidemic and less than 10% show type III hyperlipoproteinemia.

    “most of homozygous APOE2 carrier are normolipidemic and less than 10% of them show type III hyperlipoproteinemia [14, 15].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [14] Matsunaga A, Saito T. Apolipoprotein E mutations: a comparison between lipoprotein glomerulopathy and type III hyperlipoproteinemia. Clin Exp Nephrol. 2014;18(2):220–4. source
    • cites [15] Saito T, Matsunaga A, Fukunaga M, Nagahama K, Hara S, Muso E. Apolipoprotein E-related glomerular disorders. Kidney Int. 2020;97(2):279–88. source

  • Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.

    Premisenone given

    ApoE binds to LDL receptors or LDL receptor-related proteins and mediates the uptake of triglyceride-rich lipoproteins by hepatocytes from circulation.

    “As a vital component of various lipoproteins (chylomicrons, very low-density lipoproteins, and medium-density lipoproteins), ApoE binds to LDL receptors or LDL receptor-related proteins and mediates the uptake of triglyceride-rich lipoproteins by hepatocytes from circulation.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds. It may state two separate claims as one.

    Premisenone given

    The APOE gene of humans is located on chromosome 19 and comprised of 4 exons, encoding an N-terminal signal peptide containing 18 amino acids and a mature ApoE protein consisting of 299 amino acids.

    “The APOE gene of humans is located on chromosome 19 and comprised of 4 exons, encoding an N-terminal signal peptide containing 18 amino acids and a mature ApoE protein consisting of 299 amino acids.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim. The paper’s conclusions may not depend on it.

    Interpretationreasoning

    The APOE Chicago mutation (p.Arg165Pro) is often expressed as Arg147Pro in the mature protein.

    “Therefore, the APOE Chicago mutation (p. Arg165Pro) is often expressed as Arg147Pro in the mature protein.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds.

    Premisenone given

    LPG mutations usually do not include the major APOE mutation E2 based on the amino acid residue at site 158.

    “But the mutations usually do not include the major APOE mutation E2 based on the amino acid residue at site 158.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds. It may state two separate claims as one.

    Premisenone given

    LPG is an extremely rare disease with most cases in Eastern Asia.

    “LPG is an extremely rare disease with most cases in Eastern Asia.”
    Quote in the paperNot a substantial claim
31 of 31

Citations

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Research works printed but not linked: 1

  1. Wei Y, Yao J, Zhang P, Gao C, He X, Jia L, et al. Lipoprotein glomerulopathy caused by mutation of apolipoprotein E gene in children: a report of two cases. Chin J Nephrol. 2023;39(3):215–219.[in Chinese]

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Authors
Liu, Y., Cheng, Y., Wen, Y., Li, C., Chen, G., & Li, M.
Affiliations
Chinese Academy of Medical Sciences & Peking Union Medical College (CN)
Corresponding author
Li, Mingxi
ORCID
Venue
BMC Nephrology
Publisher
Springer Science and Business Media LLC
Published
2024-03-06
Volume
25
Issue
1
Pages
87-87
ISSN
1471-2369 (ISSN-L)
DOI
10.1186/s12882-024-03515-z
PMC
PMC10918868
OpenAlex
W4392507246
Semantic Scholar
fde513afdf2a238dfd1511d0c52bc9275783e9d1
Cited by
2
References
21
Citations by year
2026: 2
FWCI
0.57
Type
journal article
Language
en
Open access
Licence
Locations
  • BMC Nephrology (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
Funders
National High Level Hospital Clinical Research Funding (2022-PUMCH-B-021)
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, APOE gene, nephrotic syndrome, hyperlipidemia, triglyceride elevation, podocyte foot process fusion, incomplete penetrance, familial inheritance, fenofibrate, lipid-lowering therapy, renal biopsy, genetic diagnosis
MeSH terms
Adolescent, Apolipoproteins E, Chicago, Humans, Kidney Diseases, Male, Nephrotic Syndrome

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.

A language model drew the claims from the paper on 2026-10-31, under version 3 of the claim definition (model deepseek-v4.1-flash, prompt extract-v3).

A second model labelled each claim on 2026-10-31 (model jev-1.13-20260917, definition revision gold-guideline-v0.2).

Cited sources are checked with a language model’s help (gpt-6-sol).

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 ›

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