Apolipoprotein E–related glomerular disorders

Saito, Takao; Matsunaga, Akira; Fukunaga, Masao; Nagahama, Kiyotaka; Hara, Shigeo; Muso, Eri

doi:10.1016/j.kint.2019.10.031

Cited by 46 publications

(58 citation statements)

References 104 publications

(151 reference statements)

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“…Lipoprotein glomerulopathy (LPG) is a renal disease in which lipid deposition is limited to the kidney and is believed to cause glomerulosclerosis. This disease is characterized by glomerular lipoprotein thrombi and clinically by proteinuria and type III hyperlipoproteinemia with apoE abnormality [21,28]. The elevated plasma apoE concentration caused by reduced receptor-binding activity is an important determinant for the development of LPG.…”

Section: Apoe and Lipoprotein Glomerulopathy (Lpg)mentioning

confidence: 99%

“…Furthermore, many glomerular disorders caused by abnormalities in apoE-containing lipoproteins have been identified. Of these disorders, lipoprotein glomerulopathy and apoE2 homozygote glomerulopathy have been characterized and differentiated histologically [21]. However, both disorders present with a lipid profile similar to FD [21].…”

Section: Overlaps Between Adh Fchl Fd and Lpgmentioning

confidence: 99%

“…Of these disorders, lipoprotein glomerulopathy and apoE2 homozygote glomerulopathy have been characterized and differentiated histologically [21]. However, both disorders present with a lipid profile similar to FD [21]. In fact, apoE homozygosity is considered responsible for FD, but only 10 cases of apoE2 homozygote glomerulopathy were reported worldwide.…”

Section: Overlaps Between Adh Fchl Fd and Lpgmentioning

confidence: 99%

“…In addition to the three major isoforms apoE2, E3 and E4, three minor apoE isoforms have been observed by isoelectric focusing, E1, E5, and E7, each one presenting several nucleotide sequence variants with different amino acid substitutions [21]. The minor E1 isoform has an isoelectric point more acid, by two units of charge, than apoE3 due to either p.Lys164Glu, p.Arg168Gly-E2, p.Gln174_Gly190del variants (Table 1).…”

Section: Introductionmentioning

confidence: 99%

“…Moreover, rare apoE mutants have been associated with different dyslipidemias such as familial dysbetalipoproteinemia (FD, type III) (OMIM # 617347), familial combined hyperlipidaemia (FCHL, type IIb) (OMIM # 144250), ADH (type IIa), hypertriglyceridemia (HTG, type IV and V), lipoprotein glomerulopathy (LPG) (OMIM #611771) [21,28], sea-blue histiocytosis (OMIM #269600) [29] or late-onset Alzheimer disease (OMIM # 104310) [30].…”

Section: Introductionmentioning

confidence: 99%

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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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Section: Apoe and Lipoprotein Glomerulopathy (Lpg)mentioning

confidence: 99%

Section: Overlaps Between Adh Fchl Fd and Lpgmentioning

confidence: 99%

Section: Overlaps Between Adh Fchl Fd and Lpgmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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APOE gene variants in primary dyslipidemia

et al. 2021

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Immune landscape and the key role of APOE+ monocytes of lupus nephritis under the single‐cell and spatial transcriptional vista

Tang

Zhang

et al. 2023

Clinical & Translational Med

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Background Lupus nephritis (LN) is among the most common complication of systemic lupus erythematosus (SLE) with high mortality and morbidity. The analysis of LN kidney's local immune response through single‐cell and spatial transcriptome enables the study of potential therapeutic targets. Methods By single cell sequencing and spatial transcriptome, we profile cells from LN kidney and normal kidney tissues to characterize cellular composition and elucidate the potential upstream monocyte/macrophage (Mono/MΦ) initiating the auto‐immune response. After the high‐throughput synergy screening, we performed the immunofluorescence to identify the specific cells in LN patients. The function experiments were finished by flow cytometry and Elisa. Results By immunofluorescence and spatial transcriptome, we identified differential subsets of Mono/MΦ and demonstrated that they exhibit temporal expression of TIMP1, IL1B, SPP1 and APOE. With the function experiments, we found that the APOE+ Mono may be compensatorily increased in LN, and the capacity of antigen presenting was decreased with the overexpression of APOE. Furthermore, how do the LN‐specific Mono/MΦ transport in and out the glomerulus to active the local immune response remains unclear. Our results showed that lymphangiogenesis occurred in LN kidneys but not in normal kidneys, suggesting the presence of a new lymphatic vessel may serve as a ‘green channel’ for LN‐specific Mono/MΦ. Conclusions In LN, APOE+ Mono are compensatorily elevated, with decreased antigen presenting ability and reduced secretion of interferons. The lymphangiogenesis in LN prompts the trafficking of Mono/MΦ in LN kidney.

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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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Apolipoprotein E–related glomerular disorders

Cited by 46 publications

References 104 publications

APOE gene variants in primary dyslipidemia

APOE gene variants in primary dyslipidemia

Immune landscape and the key role of APOE+ monocytes of lupus nephritis under the single‐cell and spatial transcriptional vista

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

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