CEN Case Reports

, Volume 7, Issue 2, pp 225–228 | Cite as

Focal segmental glomerulosclerosis with heterozygous apolipoprotein E5 (Glu3Lys)

  • Masaru Sasaki
  • Tetsuhiko YasunoEmail author
  • Kenji Ito
  • Akira Matsunaga
  • Satoshi Hisano
  • Yasuhiro Abe
  • Katsuhisa Miyake
  • Kosuke Masutani
  • Hitoshi Nakashima
  • Takao Saito
Case Report


Apolipoprotein (apo) E5 is a rare apoE isoform. The apoE5 (Glu3Lys) variant, which is caused by the substitution of lysine with glutamic acid at codon 3, has a relative frequency of 0.1% in Japan. Previous studies have reported that apoE5 (Glu3Lys) is associated with hyperlipidemia and cardiovascular diseases, but this isoform has higher LDL receptor-binding activity than that of normal apoE3. Nephropathy associated with apoE5 (Glu3Lys) alone has not yet been reported. We present a case of a 51-year-old man with nephrotic syndrome. On renal biopsy, three glomeruli showed segmental sclerosis with hypertrophy of podocytes and intracapillary marked infiltration of intraglomerular foam cells. These findings were compatible with focal segmental glomerulosclerosis (FSGS). The patient had mild diabetes mellitus and monoclonal gammopathy of undetermined significance, but there were no specific findings of nephrolopathy related to these diseases. Various factors are involved in the pathogenesis of FSGS, including dyslipidemia and apoE activity. Our findings suggest that abnormal lipid metabolism by ApoE5 (Glu3Lys) is involved in the onset of FSGS.


ApoE isoform Foam cells Hyperlipidemia Podocyte injury Variant 




Compliance with ethical standards

Conflict of interest

All the authors declare that there are no competing interests.

Human and animal rights statement

This article does not contain any studies with human participants performed by any of the authors.

Informed consent

Written informed consent was obtained from the patient before commencement of the phenotype and gene analyses of apoE.


  1. 1.
    Matsunaga A, Sasaki J, Moriyama K, et al. Population frequency of apolipoprotein E5 (Glu3→Lys) and E7 (Glu244→Lys, Glu245→Lys) variants in western Japan. Clin Genet. 1995;48:93–9.CrossRefGoogle Scholar
  2. 2.
    Dong LM, Yamamura T, Yamamoto A. Enhanced binding activity of an apolipoprotein E mutant, APO E5, to LDL receptors on human fibroblasts. Biochem Biophys Res Commun. 1990;168:409–14.CrossRefGoogle Scholar
  3. 3.
    Dong LM, Yamamura T, Tajima S, Yamamoto A. Site-directed mutagenesis of an apolipoprotein E mutant, apo E5(Glu3→Lys) and its binding to low density lipoprotein receptors. Biochem Biophys Res Commun. 1992;187:1180–6.CrossRefGoogle Scholar
  4. 4.
    Kodera H, Mizutani Y, Sugiyama S, et al. A case of lipoprotein glomerulopathy with ApoE Chicago and ApoE (Glu3Lys) treated with fenofibrate. Case Rep Nephrol Dial. 2017;7(2):112–20.CrossRefGoogle Scholar
  5. 5.
    Takasaki S, Matsunaga A, Joh K, Saito T. A case of lipoprotein glomerulopathy with a rare apolipoprotein E isoform combined with neurofibromatosis type I. CEN Case Rep. 2018;7(1):127–31.CrossRefGoogle Scholar
  6. 6.
    Meyrier A. Mechanisms of disease: focal segmental glomerulosclerosis. Nat Clin Pract Nephrol. 2005;1:44–54.CrossRefGoogle Scholar
  7. 7.
    Diamond JR, Karnovsky MJ. Focal and segmental glomerulosclerosis: analogies to atherosclerosis. Kidney Int. 1988;33:917–24.CrossRefGoogle Scholar
  8. 8.
    Bruschi M, Catarsi P, Candiano G, et al. Apolipoprotein E in idiopathic nephrotic syndrome and focal segmental glomerulosclerosis. Kidney Int. 2003;63:686–95.CrossRefGoogle Scholar
  9. 9.
    Saito T, Atkins RC. Contribution of mononuclear leucocoytes to the progression of experimental focal glomerular sclerosis. Kidney Int. 1990;37:1076–83.CrossRefGoogle Scholar
  10. 10.
    Saito T, Ootaka T, Sato H, et al. Participation of macrophages in segmental endocapillary proliferation preceding focal glomerular sclerosis. J Pathol. 1993;170:179–85.CrossRefGoogle Scholar
  11. 11.
    Tudorache IF, Trusca VG, Gafencu AV. Apolipoprotein E—a multifunctional protein with implications in various pathologies as a result of its structural features. Comput Struct Biotechnol J. 2017;15:359–65.CrossRefGoogle Scholar
  12. 12.
    Kawanishi K, Sawada A, Ochi A, et al. Glomerulopathy with homozygous apolipoprotein E2: A report of tree cases and review of the literature. Case Rep Nephrol Urol. 2013;3:128–35.CrossRefGoogle Scholar
  13. 13.
    Saito T, Matsunaga A, Oikawa S. Impact of lipoprotein glomerulopathy on the relationship between lipids and renal diseases. Am J Kidney Dis. 2006;47:199–211.CrossRefGoogle Scholar

Copyright information

© Japanese Society of Nephrology 2018

Authors and Affiliations

  • Masaru Sasaki
    • 1
  • Tetsuhiko Yasuno
    • 1
    Email author
  • Kenji Ito
    • 1
  • Akira Matsunaga
    • 2
  • Satoshi Hisano
    • 3
  • Yasuhiro Abe
    • 1
  • Katsuhisa Miyake
    • 1
  • Kosuke Masutani
    • 1
  • Hitoshi Nakashima
    • 1
  • Takao Saito
    • 4
  1. 1.Division of Nephrology and Rheumatology, Department of Internal Medicine, Faculty of MedicineFukuoka UniversityFukuokaJapan
  2. 2.Department of Laboratory Medicine, Faculty of MedicineFukuoka UniversityFukuokaJapan
  3. 3.Department of Pathology, Faculty of MedicineFukuoka UniversityFukuokaJapan
  4. 4.Sanko ClinicFukuokaJapan

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