A novel apolipoprotein E mutation, ApoE Tsukuba (Arg 114 Cys), in lipoprotein glomerulopathy

Hagiwara, Masahiro; Yamagata, Kunihiro; Matsunaga, Tsuneaki; Arakawa, Yoh; Usui, Joichi; Shimizu, Yoshio; Aita, Kumi; Nagata, Michio; Kôyama, Akio; Zhang, Bo; Mastunaga, Akira; Saku, K.; Saito, Takao

doi:10.1093/ndt/gfm735

Cited by 22 publications

(22 citation statements)

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“…After treatment, both patients showed a remarkable decrease in urinary protein excretion, improvement in hyperlipidemia, and disappearance of the lipoprotein thrombi in the glomeruli by renal biopsy after 11 months to 2 years. The clinical effectiveness of fibrates was reported in two other patients [21,22]. We initially treated the patient with probucol, enalapril, and dipyridamole and found a decrease in the level of ApoE for a 1-year period.…”

Section: Discussionmentioning

confidence: 91%

Improvement of nephrotic syndrome by intensive lipid-lowering therapy in a patient with lipoprotein glomerulopathy

et al. 2009

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Lipoprotein glomerulopathy (LPG) is a rare hereditary disease characterized by the accumulation of much thrombi material consisting of lipoproteins at the glomerular capillary lumen. Most patients show nephrotic syndrome; nearly half progress to chronic renal failure. Intensive therapy with lipid-lowering agents reportedly engenders clinical remission with histological resolution. We report the case of a 14-year-old Japanese female patient who had been in a nephrotic condition with hematuria from 4 years old and who had been diagnosed based on pathological and molecular examination at 7 years old. We initially treated the patient with probucol, enalapril (angiotensin-converting enzyme inhibitor: ACEI), and dipyridamole from age 7, but achieved no improvement in her nephrotic status. Subsequently, we replaced probucol with bezafibrate at age 11 and added atorvastatin calcium hydrate and valsartan (angiotensin II receptor blocker: ARB) the following year. The next 3 years' treatment improved her nephrotic status, decreased serum apolipoprotein E, and markedly decreased intraglomerular lipoprotein thrombi. Early and intensive therapy with antilipidemic drugs combined with ACEI and ARB is inferred to be effective for LPG.

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Section: Discussionmentioning

confidence: 91%

Improvement of nephrotic syndrome by intensive lipid-lowering therapy in a patient with lipoprotein glomerulopathy

et al. 2009

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“…PCR products were then electrophoresed as described above (Figure 2). To verify the correct APOE ε7 allele, the nucleotide sequence of the APOE gene was analyzed using the E7 primer (5′-CGTGAATTCGCATGGCTGCAGGCTTCGGCGTTC-3′) and the common primer E9, which covered exon 4 of the APOE 5,16–18…”

Section: Methodsmentioning

confidence: 99%

<em>Apolipoprotein ε7 </em>allele in memory complaints: insights through protein structure prediction

Youn¹,

Lim

Han³

et al. 2017

CIA

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PurposeAPOE ε7 gene is a rare mutant form of APOE ε3. The mutation occurs in the lipid-binding domain of APOE. Based on the protein’s structure, APOE ε7 is expected to function in lipid and β-amyloid metabolism, similar to APOE ε4. However, unlike that for APOE ε4, the mechanisms responsible for Alzheimer’s disease (AD) cases associated with APOE ε7 expression have not been elucidated. The present study aims to investigate the association between APOE ε7 expression and cognitive impairment.MethodsAPOE was sequenced in DNA samples collected from 344 memory-complaint patients who visited the memory clinic, and from 345 non-memory-complaint individuals from the health promotion center. The protein structures of ApoE3, ApoE4, and ApoE7 were predicted.ResultsThree ε3/ε7 heterozygote individuals who were all classified under the memory-complaint group were identified. Of these, two subjects were clinically diagnosed with AD with small vessel disease, and the remaining individual was diagnosed with subjective cognitive impairment. This study predicted the protein structures of ApoE3, ApoE4, and ApoE7 and determined the three-dimensional structure of the carboxy terminus of ApoE7, which participates in an electrostatic domain interaction similar to that of APOE ε4. APOE K244 or K245 mutations for APOE ε7 were not found in the Korean reference genome database, which contains information (http://152.99.75.168/KRGDB/browser/mainBrowser.jsp) from 622 healthy individuals.ConclusionAs verified by the results of structural prediction, APOE ε7 could serve as another risk factor for cognitive impairment and is particularly associated with vascular disease. However, additional studies are required to validate the pathogenic nature of APOE ε7.

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“…Z Hu et al: APOE Kyoto mutation assembled in China c l i n i c a l i n v e s t i g a t i o n Ninety LPG cases have been reported worldwide, 4,9,10,17,[19][20][21][24][25][26][27][28][29][30][31][32][33] nine with the APOE Kyoto mutation. 8,14,[16][17][18][19][20][21] Herein, we presented 35 LPG patients carrying the APOE Kyoto allele, making it the most common mutation related to LPG.…”

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confidence: 99%

Hereditary features, treatment, and prognosis of the lipoprotein glomerulopathy in patients with the APOE Kyoto mutation

Huang

et al. 2014

Kidney International

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Lipoprotein glomerulopathy is a rare inherited renal disease, caused by mutation of the APOE gene, characterized by proteinuria and nephrotic syndrome with elevated serum apoE. Since its treatment and outcome are unknown, we retrospectively studied 35 patients within 31 unrelated Han families with biopsy-proven lipoprotein glomerulopathy residing in the same county in southwest China. DNA sequencing detected the APOE Kyoto mutation (p. Arg25Cys) in all patients and 28 asymptomatic relatives. All shared the same ɛ3 allele. The patients presented with proteinuria, higher total triglyceride, and serum apoE levels relative to non-carriers. The serum apoE and triglyceride levels of asymptomatic carriers were between those of the patients and non-carriers. Sixteen patients received fenofibrate treatment for over 12 months. Six reached complete remission (proteinuria under 0.3 g/day with stable serum creatinine) with intensive control of their lipid profile (normalized serum apoE and triglycerides under 100 mg/dl). Eight reached partial remission. At 3 years of follow-up, patients treated with fenofibrate had superior survival and stable renal function. Thus, fenofibrate can induce lipoprotein glomerulopathy remission and the fibrate effects depend on the degree of lipid control and baseline proteinuria. Moreover, normalization of serum apoE and triglycerides can be used to judge the efficacy of lipid-lowering treatment.

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A novel apolipoprotein E mutation, ApoE Tsukuba (Arg 114 Cys), in lipoprotein glomerulopathy

Cited by 22 publications

References 12 publications

Improvement of nephrotic syndrome by intensive lipid-lowering therapy in a patient with lipoprotein glomerulopathy

Improvement of nephrotic syndrome by intensive lipid-lowering therapy in a patient with lipoprotein glomerulopathy

<em>Apolipoprotein ε7 </em>allele in memory complaints: insights through protein structure prediction

Hereditary features, treatment, and prognosis of the lipoprotein glomerulopathy in patients with the APOE Kyoto mutation

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A novel apolipoprotein E mutation, ApoE Tsukuba (Arg 114 Cys), in lipoprotein glomerulopathy

Cited by 22 publications

References 12 publications

Improvement of nephrotic syndrome by intensive lipid-lowering therapy in a patient with lipoprotein glomerulopathy

Improvement of nephrotic syndrome by intensive lipid-lowering therapy in a patient with lipoprotein glomerulopathy

<em>Apolipoprotein &epsilon;7 </em>allele in memory complaints: insights through protein structure prediction

Hereditary features, treatment, and prognosis of the lipoprotein glomerulopathy in patients with the APOE Kyoto mutation

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<em>Apolipoprotein ε7 </em>allele in memory complaints: insights through protein structure prediction