Significance of a Novel Apolipoprotein E Variant, ApoE Osaka/Kurashiki, in Lipoprotein Glomerulopathy

Saito, Takao; Matsunaga, Akira

doi:10.5551/jat.10165

Cited by 5 publications

(3 citation statements)

References 11 publications

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“…By Sanger sequencing of APOE , we found three APOE mutations including APOE ‐Kyoto (R25C), APOE ‐Osaka/Kurashiki (R158P) and APOE ‐Chicago (R147P). For the first time we report APOE ‐Osaka/Kurashiki outside of Japan (Saito & Matsunaga, 2011). APOE ‐Chicago was also first reported in Chinese LPG patients which was first reported in a male Mexican‐American patient (Sam et al., 2006) and later in a Japanese female patient (Kodera et al., 2017).…”

Section: Discussionmentioning

confidence: 99%

Clinical and genetic analysis of lipoprotein glomerulopathy patients caused by APOE mutations

Mingxin

Weng

Pan

et al. 2020

Molec Gen & Gen Med

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Background Lipoprotein glomerulopathy (LPG) is a rare kidney disease caused by APOE mutations. The aim of this study was to correlate the genetic and clinical features of LPG. Methods Totally eight LPG patients were recruited in this study and Sanger sequencing of APOE was performed for all available family members. Clinical and histological features were analyzed. A literature review of LPG was also conducted. Results Genetic analysis revealed five patients with APOE‐ Kyoto, two with APOE‐ Osaka/Kurashiki, and one with APOE‐ Chicago mutations. LPG patients with urine protein reduced more than 50% had a slower decrease in renal function than those with less urine protein reduction (estimated glomerular filtration rate reduction rate −5.0 ± 0.8 vs. 1.5 ± 0.7 ml/min per 1.73 m 2 ⋅month −1 , p = .03). We then enrolled 95 LPG patients from previous studies and this study. LPG patients had higher blood pressure (mean arterial pressure: 109.4 ± 19.4 vs. 94.4 ± 11.1 mmHg, p < .001) than the control group. Interestingly, patients with APOE mutations in the LDL receptor binding region had higher serum apolipoprotein E (apoE) levels [ln(apoE): 2.7 ± 0.4 vs. 2.0 ± 0.5 mg/dl, p < .001] in comparison to other domains. Conclusion Here, we report for the first time APOE ‐Osaka/Kurashiki and APOE ‐Chicago mutations in the Chinese population. LPG was associated with higher blood pressure and serum apoE levels were higher in patients with mutations in LDL receptor binding region. In addition, the findings further indicated that treatment of proteinuria might slow down renal function progression in these patients.

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Section: Discussionmentioning

confidence: 99%

Clinical and genetic analysis of lipoprotein glomerulopathy patients caused by APOE mutations

Mingxin

Weng

Pan

et al. 2020

Molec Gen & Gen Med

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“…Most of these mutations are located in, or close to, the LDL receptor-binding domain 1 , 4 , 5 , 9 , 19 , 21 , 22 , 23 , 24. Among the missense mutations, four are proline, four are arginine substitutions (at position 145, 147, 150, and 158 of the mature protein), and three are cysteine for arginine substitutions (at position 25, 114, and 150 of the mature protein) 4 , 7 , 8 , 19 , 25 , 26 , 27 , 28. Deletions involve the region encompassing the amino acid residues 141-146 (141-143, 142-144, and 144-146 in the central region of the binding domain) or the region encompassing the amino acid residues 156-173 (which includes the Arg172 residue involved in the binding to LDL receptor) 13 , 15 , 17 , 19 , 20 , 23 , 29 , 30.…”

Section: Introductionmentioning

confidence: 99%

“…Podocyte damage is related to proteinuria/nephrotic syndrome, and mesangial hipercellularity is associated to double contour. The mutations of ApoE more frequently implicated with LPG are ApoE Sendai (Arg145Pro), ApoE Kyoto (Arg25Cys), ApoE Tokyo, ApoE1, ApoE Guangzhou (Arg150Pro), ApoE Maebashi, ApoE Tsukuba, ApoE Chicago, and ApoE Okayama 4 , 6 , 15 , 23 , 26 , 30 , 34. Abnormal apoE proteins determine mesangial and basement membrane alterations, which are associated to increased glomerular permeability and nephrotic syndrome with higher levels of LDL, VLDL, and apolipoproteins B, C-II, and C-III.…”

Section: Introductionmentioning

confidence: 99%

Pathogenesis, histopathologic findings and treatment modalities of lipoprotein glomerulopathy: A review

Cambruzzi

Pêgas

2019

J. Bras. Nefrol.

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Lipoprotein glomerulopathy (LPG) is an uncommon cause of nephrotic syndrome and/or kidney failure. At microscopy, LPG is characterized by the presence of lipoprotein thrombi in dilated glomerular capillaries due to different ApoE mutations. ApoE gene is located on chromosome 19q13.2, and can be identified in almost all serum lipoproteins. ApoE works as a protective factor in atherosclerosis due its interaction with receptor-mediated lipoprotein clearance and cholesterol receptor. Most common polymorphisms include ApoE2/2, ApoE3/2, ApoE3/3, ApoE4/2, ApoE4/3, and ApoE4/4. All age-groups can be affected by LPG, with a discrete male predominance. Compromised patients typically reveal dyslipidemia, type III hyperlipoproteinemia, and proteinuria. LPG treatment includes fenofibrate, antilipidemic drugs, steroids, LDL aphaeresis, plasma exchange, antiplatelet drugs, anticoagulants, urokinase, and renal transplantation. Recurrence in kidney graft suggests a pathogenic component(s) of extraglomerular humoral complex resulting from abnormal lipoprotein metabolism and presumably associated to ApoE.

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APOE gene variants in primary dyslipidemia

et al. 2021

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Apolipoprotein E (apoE) is a major apolipoprotein involved in lipoprotein metabolism. It is a polymorphic protein and different isoforms are associated with variations in lipid and lipoprotein levels and thus cardiovascular risk. The isoform apoE4 is associated with an increase in LDL-cholesterol levels and thus a higher cardiovascular risk compared to apoE3. Whereas, apoE2 is associated with a mild decrease in LDL-cholesterol levels. In the presence of other risk factors, apoE2 homozygotes could develop type III hyperlipoproteinemia (familial dysbetalipoproteinemia or FD), an atherogenic disorder characterized by an accumulation of remnants of triglyceride-rich lipoproteins. Several rare APOE gene variants were reported in different types of dyslipidemias including FD, familial combined hyperlipidemia (FCH), lipoprotein glomerulopathy and bona fide autosomal dominant hypercholesterolemia (ADH). ADH is characterized by elevated LDL-cholesterol levels leading to coronary heart disease, and due to molecular alterations in three main genes: LDLR, APOB and PCSK9. The identification of the APOE-p.Leu167del variant as the causative molecular element in two different ADH families, paved the way to considering APOE as a candidate gene for ADH. Due to non mendelian interacting factors, common genetic and environmental factors and perhaps epigenetics, clinical presentation of lipid disorders associated with APOE variants often strongly overlap. More studies are needed to determine the spectrum of APOE implication in each of the diseases, notably ADH, in order to improve clinical and genetic diagnosis, prognosis and patient management. The purpose of this review is to comment on these APOE variants and on the molecular and clinical overlaps between dyslipidemias.

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Significance of a Novel Apolipoprotein E Variant, ApoE Osaka/Kurashiki, in Lipoprotein Glomerulopathy

Cited by 5 publications

References 11 publications

Clinical and genetic analysis of lipoprotein glomerulopathy patients caused by APOE mutations

Clinical and genetic analysis of lipoprotein glomerulopathy patients caused by APOE mutations

Pathogenesis, histopathologic findings and treatment modalities of lipoprotein glomerulopathy: A review

APOE gene variants in primary dyslipidemia

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