Skip to main content

Advertisement

SpringerLink
Log in

ACE I/D gene polymorphism in primary FSGS and steroid-sensitive nephrotic syndrome

  • Original Article
  • Published:
Pediatric Nephrology Aims and scope Submit manuscript

Abstract

The role of angiotensin-converting enzyme (ACE) insertion/deletion (I/D) gene polymorphism in various renal disorders has been investigated. We evaluated the association between the clinical characteristics and ACE genotypes of Turkish children with primary focal segmental glomerulosclerosis (FSGS) and steroid-sensitive nephrotic syndrome (SSNS). Patients with FSGS (n=30) were classified into two groups: one with remission together with stable renal function (n=22) and the other without remission and with impaired renal function (n=8). We classified children with SSNS (n=43) that were followed for at least 4 years into two subgroups as having more frequent (n=19) and less frequent relapses (n=11). The DD genotype was more frequent in the SSNS group than that in controls (37% vs. 17%, χ 2=4.98, P=0.025). However, among SSNS subgroups, the frequency of the DD genotype was not different. The distribution of ACE genotype was similar among patients with FSGS and SSNS. There was no difference in the ACE I/D distribution between children with FSGS and normal controls (II 10%, ID 60%, DD 30% vs. II 13%, ID 70%, DD 17%). The frequency of the DD genotype was higher in FSGS patients with declining renal function (63%) than in those with stable renal function (18%) (P=0.031). Progressive renal impairment was significantly more frequent in patients with FSGS with the homozygous D allele compared with FSGS patients with ID and II genotypes. Our results indicate that the DD genotype may be a risk factor for the development of progressive renal impairment in children with FSGS; however, larger studies are required to confirm this.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Clark AG, Barratt TM (1999) Steroid-responsive nephrotic syndrome. In: Barratt TM, Avner ED, Harmon WE (eds) Pediatric nephrology. Lippincott Williams and Wilkins, Baltimore, pp 731–746

  2. Cortes L, Tejani A (1996) Dilemma of focal segmental glomerular sclerosis. Kidney Int [Suppl 53]:S57–S63

  3. Schwartz MM, Korbet SM (1993) Primary focal segmental glomerulosclerosis: pathology, histologic variants, and pathogenesis. Am J Kidney Dis 22:874–883

    CAS  PubMed  Google Scholar 

  4. Frishberg Y, Becker-Cohen R, Halle D, Feigin E, Eisenstein B, Halevy R, Lotan D, Juabeh I, Ish-Sholom N, Magen D, Shvil Y, Sinai-Treiman L, Drukker A (1998) Genetic polymorphisms of the renin-angiotensin system and the outcome of focal segmental glomerulosclerosis in children. Kidney Int 54:1843–1849

    Article  CAS  PubMed  Google Scholar 

  5. Aucella F, Vigilanta M, Margaglione M, Grandone E, Popolo A del, Forcella M, Procaccini D, Salatino G, Passione A, Ktena M, DeMin A, Stallone C (2000) Polymorphism of the angiotensin-converting enzyme gene in end-stage renal failure patients. Nephron 85:54–59

    Article  CAS  PubMed  Google Scholar 

  6. Lafayette RA, Mayer G, Park SK, Meyer TW (1992) Angiotensin II receptor blockade limits glomerular injury in rats with reduced renal mass. J Clin Invest 90:766–771

    CAS  PubMed  Google Scholar 

  7. Lee D, Kim W, Kang S, Koh GY, Park SK (1997) ACE gene polymorphism in patients with minimal change nephrotic syndrome and focal segmental glomerulosclerosis. Nephron 77:471–473

    CAS  PubMed  Google Scholar 

  8. Matsusaka T, Hymes J, Ichikawa I (1996) Angiotensin in progressive renal diseases: theory and practice. J Am Soc Nephrol 7:2025–2041

    CAS  PubMed  Google Scholar 

  9. Gomez RA, El-Dahr S, Chevalier RL (1999) Vasoactive hormones. In: Barratt TM, Avner ED, Harmon WE (eds) Pediatric nephrology. Lippincott Williams and Wilkins, Baltimore, pp 83–90

  10. Hohenfellner K, Hunley TE, Brezinska R, Brohhag P, Shyr Y, Brenner W, Habermehl P, Kon V (1999) ACE I/D gene polymorphism predicts renal damage in congenital uropathies. Pediatr Nephrol 13:514–518

    CAS  PubMed  Google Scholar 

  11. Al-Eisa A, Haider MZ, Srivasta BS (2001) Angiotensin converting enzyme gene insertion/deletion polymorphism in idiopathic nephrotic syndrome in Kuwaiti Arab children. Scand J Urol Nephrol 35:239–242

    Article  CAS  PubMed  Google Scholar 

  12. Fujisawa T, Ikegma H, Kawaguchi Y, Hamada Y, Ueda H, Shintani M, Fukuda M, Ogihara T (1998) Meta-analysis of association of insertion/deletion polymorphism of angiotensin I converting enzyme gene with diabetic nephropathy and retinopathy. Diabetologia 41:47–53

    Article  CAS  PubMed  Google Scholar 

  13. Özen S, Alikasifoglu M, Saatçı U, Bakkaloğlu A, Besbas N, Kara N, Kocak H, Erbas B,Unsal I, Tuncbilek E (1999) Implication of certain genetic polymorphism in scarring in vesicoureteric reflux: importance of ACE polymorphism Am J Kidney Dis 34:140–145

    Google Scholar 

  14. Stratta P, Canavese C, Ciccone G, Barolo S, Dall’Omo AM, Fasano ME, Mazzola G, Berutti S, Fop F, Curtoni ES, Piccoli G (1999) Angiotensin I-converting enzyme genotype significantly affects progression of IgA glomerulonephritis in an Italian population. Am J Kidney Dis 33:1071–1079

    CAS  PubMed  Google Scholar 

  15. A report of the International Study of Kidney Disease in Children (1978) Nephrotic syndrome in children: prediction of histopathology from clinical and laboratory characteristics at time of diagnosis. Kidney Int 13:159–165

    PubMed  Google Scholar 

  16. Horan MJ, Sinaiko AR (1987) Synopsis of the report of the Second Task Force on Blood Pressure Control in children. Hypertension 10:115–121

    CAS  PubMed  Google Scholar 

  17. Schwartz GJ, Brion LP, Spitzer A (1987) The use of plasma creatinine concentration for estimating glomerular filtration rate in infants, children and adolescents. Pediatr Clin North Am 34:571–590

    CAS  PubMed  Google Scholar 

  18. Kawasaki ES (1990) Sample preparation from blood, cells, and other fluids. In Michael A, Gelfand DH, Sninsky JJ, White TJ (eds) PCR protocols: a guide to methods and applications. San Diego, pp 146–152

  19. Rigat B, Hubert C, Corvol P, Subrier F (1990) PCR detection of the insertion/deletion polymorphism of the human angiotensin converting enzyme gene (DCPI) (dipeptylcarboxypeptidase I). Nucleic Acids Res 20:1433

    Google Scholar 

  20. Lindpaintner K, Pfeffer MA, Kreutz R, Stampfer MJ, Grodstein F, LaMotte F, Buring J, Hennekens H (1995) A prospective evaluation of an angiotensin-converting enzyme gene polymorphism and the risk of ischemic heart disease. N Engl J Med 332:706–711

    CAS  PubMed  Google Scholar 

  21. Norusis MJ (1993) SSPS for windows: base system user’s guide, release 6.0. SPSS, Chicago

    Google Scholar 

  22. Navis G, Kleij FGH van der, Zeeuw D de, Jong PE de (1999) Angiotensin-converting enzyme gene I/D polymorphism and renal disease. J Mol Med 77:781–791

    Article  CAS  PubMed  Google Scholar 

  23. Schmidt A, Kiener HP, Barnas U, Arias I, Illievich A, Auinger M, Graninger W, Kaider A, Mayer G (1996) Angiotensin-converting enzyme polymorphism in patients with terminal renal failure. J Am Soc Nephrol 7:314–317

    CAS  PubMed  Google Scholar 

  24. Siragy HM (2000) Minimizing the progression of kidney disease. AT1 and AT2 receptors in the kidney: role in disease and treatment. Am J Kidney Dis 36:2–8

    Google Scholar 

  25. Navis G, Jon g P, Zeeuw D (1997) I/D polymorphism of the angiotensin converting enzyme gene: a clue to the heterogeneity in the progression of the renal disease and in the renal response to therapy? Nephrol Dial Transplant 12:1097–1100

    Article  CAS  PubMed  Google Scholar 

  26. Chen X, Liu S, Ye Y, Xu Q (1997) Association of angiotensin-converting enzyme gene insertion/deletion polymorphism with the clinicopathological manifestations in immunoglobulin A nephropathy patients. Chin Med J 11:526–529

    Google Scholar 

  27. Maruyama K, Yoshida M, Nishio H, Shirakawa T, Kawamura T, Tanaka R, Nakamura H, Iijima K, Yoshikawa N (2001) Polymorphisms of renin-angiotensin system genes in childhood IgA nephropathy. Pediatr Nephrol 16:350–355

    CAS  PubMed  Google Scholar 

  28. Civici F, Nayır A, Bilge I, Oktem F, Emre S, Sirin A (2000) Polymorphisms in angiotensin-converting enzyme gene in membranoproliferative glomerulonephritis and poststreptococcal acute glomerulonephritis patients (abstract). Abstracts of the 34th Annual Meeting of the European Society for Pediatric Nephrology, Helsinki 18–20 June 2000, p111

  29. Parsa A, Peden E, Lum RF, Seligman VA, Olson JL, Li H, Seldin MF, Criswell LA (2002) Association of angiotensin-converting enzyme polymorphisms with systemic lupus erythematosus and nephritis: analysis of 644 SLE families. Genes Immun 3 [Suppl 1]:S42–S46

  30. Lau YK, Woo KT, Choong HL, Zhao Y, Tan HB, Cheung W, Yap HK (2002) ACE gene polymorphism and disease progression of IgA nephropathy in Asians in Singapore. Nephron 91:499–503

    Article  CAS  PubMed  Google Scholar 

  31. Schena FP, D’Altri C, Cerullo G, Manno C, Gesualdo L (2001) ACE gene polymorphism and IgA nephropathy: an ethnically homogeneous study and a meta-analysis. Kidney Int 60:732–740

    CAS  PubMed  Google Scholar 

  32. Kunz R, Bork JP, Fritsche L, Ringel J, Sharma AM (1998) Association between the angiotensin converting enzyme insertion/deletion polymorphism and diabetic nephropathy: a methodological appraisal and systematic review. J Am Soc Nephrol 9:1953–1663

    Google Scholar 

  33. Perrichot R, Raguenes O, Mercier B, Whebe B, Lenormand JP, Ferec C, Clede J (1996) Genetic variation in the renin-angiotensin system and membranous glomerulonephritis. J An Soc Nephrol 7:1779A

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Pediatric Nephrology, School of Medicine, Suleyman Demirel University, Isparta, Turkey

    Faruk Őktem

  2. Department of Pediatric Nephrology, Istanbul Medical Faculty, University of Istanbul, Turkey

    Aydan Şirin, Ilmay Bilge & Sevinç Emre

  3. Department of Molecular Medicine, Institute of Experimental Medical Research, University of Istanbul, Turkey

    Bedia Ağaçhan & Turgay Ispir

Authors
  1. Faruk Őktem
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Aydan Şirin
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ilmay Bilge
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Sevinç Emre
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Bedia Ağaçhan
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Turgay Ispir
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Faruk Őktem.

Additional information

The abstract of this study was accepted as a poster for the 36th meeting of the European Society of Paediatric Nephrology, Bilbao, September 2002. This study was supported in part by a grant from the Istanbul University Research Fund (no T-849/17072000)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Őktem, F., Şirin, A., Bilge, I. et al. ACE I/D gene polymorphism in primary FSGS and steroid-sensitive nephrotic syndrome. Pediatr Nephrol 19, 384–389 (2004). https://doi.org/10.1007/s00467-003-1398-4

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00467-003-1398-4

Keywords

Search

Navigation