SAGE Journals Online
Advertisement
Sign In to gain access to subscriptions and/or personal tools.

 

Advanced Search

Journal Navigation

Journal Home

Subscriptions

Archive

Contact Us

Table of Contents

Advertisement

Sign In to gain access to subscriptions and/or personal tools.
Journal of Renin-Angiotensin-Aldosterone System
This Article
Right arrow Abstract Freely available
Right arrow Free Full Text (Free PDF) Free
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to Saved Citations
Right arrow Download to citation manager
Right arrowRequest Permissions
Right arrow Request Reprints
Right arrow Add to My Marked Citations
Citing Articles
Right arrow Citing Articles via Google Scholar
Right arrow Citing Articles via Scopus
Google Scholar
Right arrow Articles by Tabel, Y.
Right arrow Articles by Ytlmaz, E.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Tabel, Y.
Right arrow Articles by Ytlmaz, E.
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati   Add to Twitter  
What's this?

Effects of Genetic Polymorphisms of the Renin-Angiotensin System in Children with Nephrotic Syndrome

Ytlmaz Tabel

Department of Pediatric Nephrology, Ege University School of Medicine, Bornova, 35100, Izmir-Turkey, yilmaztabel{at}yahoo.com

Afig Berdeli

Laboratory of Molecular Medicine, Department of Pediatrics, Ege University School of Medicine, Bornova, 35100, Izmir-Turkey

Sevgi Mir

Department of Pediatric Nephrology, Ege University School of Medicine, Bornova, 35100, Izmir-Turkey

Erkin Serdaroglu

Department of Pediatric Nephrology, Ege University School of Medicine, Bornova, 35100, Izmir-Turkey

Ebru Ytlmaz

Department of Pediatric Nephrology, Ege University School of Medicine, Bornova, 35100, Izmir-Turkey

Background. The renin-angiotensin system (RAS) has been considered to be responsible for the pathogenesis or progression of many diseases which may or may not be related to kidney. Genetic polymorphisms of the various components of the RAS have been associated with differences in the clinical course of several disease states in adults and children.

Objectives. The purpose of our study was to investigate RAS gene polymorphisms in patients with steroid resistant primary focal segmental glomerulosclerosis (FSGS) and nephrotic syndrome responding to steroid therapy. Furthermore, we aimed to investigate whether there was an association between polymorphic alleles and responses to steroid therapy, the degree of renal dysfunction, and prevalence of end-stage renal disease (ESRD).

Material and methods. One hundred and fifty-eight children with the diagnosis of nephrotic syndrome were recruited from the Nephrology unit in the Department of Paediatrics of Ege University. Forty-nine of them were classified as renal biopsy-proven FSGS and 102 patients were considered to have response to steroid treatment. Renal functional impairment was detected in 19 subjects with FSGS and end-stage renal insufficiency in 13 patients. The control group consisted of 287 healthy adult subjects. Angiotensin-converting enzyme (ACE), angiotensin II type 1 receptor (AT1R) and angiotensinogen (AGT) gene polymorphisms were determined by the polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP) technique. Statistical significance was regarded as p<0.05.

Results. There were no statistically significant differences for the C allele of AT1R or the T allele of AGT genes between the children with nephrotic syndrome and control group, but on the other hand statistically significant differences were detected for D allele of ACE gene. There was no significant relationship detected between the D allele of ACE, the C allele of AT1R or the T allele of AGT genes and response to steroid therapy, extent of renal dysfunction and the progression to ESRD. However, there was a significant relationship between T allele of AGT gene and resistance to steroid treatment (OR; 4,837, 95% CI; 1,723—13,577, p=0.01), renal dysfunction (OR; 3,189, 95% CI; 0,999—10,182, p=0.041) and progression to ESRD (OR; 3,852, 95% CI; 1,057—14,040, p=0.03).

Conclusion. In this study, the angiotensino gene -235T allele was found to be related with steroid resistance, renal dysfunction and progression of ESRD in nephrotic syndrome.

Key Words: RAS • Gene polymorphism • Nephrotic syndrome • Children

References

  • Clark AG, Barrat TM Steroid-responsive nephrotic syndrome. In: Barrat TM, Avner ED, Harmon WE (eds) Pediatric nephrology. Lipincott Williams and Wilkins, Baltimore, 1999; pp 731-46.
  • Cortes L., Tejani A. Dilemma of focal segmental glomerular sclerosis. Kidney Int 1996;53:S57-S63.
  • Boyer M., Meyrier A., Niaudet P., Habib R. Minimal changes and focal segmental glomerular sclerosis. Eds: Davison AM, Cameron JS, Grünfeld JP, Kerr DNS, Ritz E and Winerals CG. Oxford Textbook of Clinical Nephrology, Oxford University Press, 1998.
  • Luther Y., Bantis C., Ivens K. et al. Effects of the genetic polymorphisms of the renin-angiotensin system on focal segmental glomerulosclerosis. Kidney Blood Press Res 2003;26:333-7.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Mezzano SA, Ruiz-Ortega M., Egido J. Angiotensin II and renal fibrosis. Hypertension 2001;38:635-8.[Abstract/Free Full Text]
  • Egido J. Vasoactive hormones and renal sclerosis. Kidney Int 1996;49:578-97.[Web of Science][Medline] [Order article via Infotrieve]
  • Frishberg Y., Becker-Cohen R., Halle D. et al. Genetic polymorphisms of the renin-angiotensin system and the outcome of focal segmental glomerulosclerosis in children. Kidney International 1998;54:1843-9.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Oktem F., Sirin A., Bilge I., Emre S., Agachan B., Ispir T. ACE I/D gene polymorphism in primary FSGS and steroid-sensitive nephrotic syndrome. Pediatr Nephrol 2004;19:384-9.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Rigat B., Hubert C., Alhenc-Gelas F., Rodby R., Gunnels JC, Soubrier F. An insertion/deletion polymorphism in the angiotensin I converting enzyme gene accounting for half the variance of serum enzyme levels. J Clin Invest 1990;86:1343-6.[Web of Science][Medline] [Order article via Infotrieve]
  • Bonnardeaux A., Davies E., Jeunemaitre X. et al. Angiotensin II type 1 receptor gene polymorphisms in human essential hypertension. Hypertension 1994;24:63-9.[Abstract/Free Full Text]
  • Jeunemaitre X., Soubrier F., Koteletsev YV et al. Molecular basis of human hypertension: Role of angiotensinogen. Cell 1992;71:169-80.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Schmidt S., Sharma AM, Zilch O. et al. Association ofM235T variant of the angiotensinogen gene with familial hypertension of early onset. Nephrol Dial Transplant 1995;10:1145-8.[Abstract/Free Full Text]
  • Morise T., Takeuchi Y., Takeda R. Rapid detection and prevalence of the variants of the angiotensinogen gene in patients with essential hypertension. J Intern Med 1995;237:175-80.of the[Web of Science][Medline] [Order article via Infotrieve]
  • Caulfield M., Lavender P., Farral M. et al. Linkage of the angiotensinogen gene to essential hypertension. N Engl J Med 1994;330:1629-33.[Abstract/Free Full Text]
  • Hingorani AD, Sharma P.,Jia H., Hopper R., Brown MJ Blood pressure and the M235T polymorphism of the angiotensinogen gene. Hypertension 1996;28:907-11.[Abstract/Free Full Text]
  • Fogarty DG, Harron JC, Hughes AE, Doherty CC, Maxwell AP The association of an angiotensinogen variant with diabetic nephropathy. (abstract) J Am Soc Nephrol 1995;6:449.
  • Schmidt S., Strojek K., Grzeszczak W., Ganten D., Ritz E. The M235T variant of the angiotensinogen gene and nephropathy in type 2 diabetes. (abstract) J Am Soc Nephrol 1995;6:1047.
  • Mendoza SA, Reznik VM, Griswold WR, Krensky AM, Yorgin PD, Tune BM Treatment of steroid-resistant focal segmental glomerulosclerosis with pulse methylprednisolone and alkylating agents. Pediatr Nephrol 1990;4:303-37.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • International study of kidney disease in children. Nephrotic syndrome in children: prediction of histopathology from clinical and laboratory characteristics at the time of diagnosis. Kidney International 1978;13:159-65.[Web of Science][Medline] [Order article via Infotrieve]
  • Update on the 1987 task force report on high blood pressure in children and adolescents: a working group report from the national high blood pressure education program. Pediatrics 1996;98:649-58.[Abstract/Free Full Text]
  • Schwartz GJ, Brion LP, Spitzer A. The use of plasma creatinine concentration for estimating glomerular filtration rate in infants, children and adolescents. Pediatr Clin North Am 1987;34:571-90.[Web of Science][Medline] [Order article via Infotrieve]
  • Russ AP, Maerz W., Ruzicka V., Stein U., Gross W. Rapid detection of the hypertension-associated Met235Thr allele of the human angiotensinogen gene. Hum Mol Genet 1993;2(5):609-10.[Free Full Text]
  • Seikaly MG, Arant BS, Seney FD Endogenous angiotensin concentrations in specific intrarenal fluid compartments in the rat. J Clin Invest 1990;86:1352-7.[Web of Science][Medline] [Order article via Infotrieve]
  • Wolf G., Bytzmann U., Wenzel UO The renin-angiotensin system and progression of renal disease: from hemodynamics to cell biology. Nephron Physiol 2003;93:3-13.
  • Wiecek A., Chudek J., Kokot F. Role of angiotensin II in the progression of diabetic nephropathy-therapeutic implications. Nephrol Dial Transplant 2003;18(suppl 5):16-20.[Free Full Text]
  • Suzuki Y., Ruiz-Ortega M., Lorenzo O., Ruperez M., Esteban V. Inflammation and angiotensin II. Int J Biochem Cell Biol 2003;35:881-900.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Lewis EJ, Hunsicker LG, Bain RP, Rohde RD for the Collaborative Study Group. The effects of angiotensin-converting enzyme inhibition of diabetic nephropathy. N Engl J Med 1993;329:1456-62.[Abstract/Free Full Text]
  • Kasiske BL, Kalil RSN, Ma JZ, Liao M., Keane WF Effects of antihypertensive therapy on the kidney in patients with diabetes: A metaregression analysis. Ann Intern Med 1993;118:129-38.[Abstract/Free Full Text]
  • Geiger H. Are angiotens in II receptor blockers superior to angiotensin converting enzyme inhibitors with regard to their renoprotective effect? Nephrol Dial Transplant 1997;12:640-2.[Free Full Text]
  • Ichikawa I. Will angiotensin II receptor antagonists be renoprotective in humans. Kidney Int 1996;50:684-92.[Web of Science][Medline] [Order article via Infotrieve]
  • Johnston CL Angiotensin receptor antagonists: focus on losartan. Lancet 1995;346:1403-07.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Ziai F., Ots M., Provoost AP et al. The angiotensin receptor antagonists, irbesartan, reduces renal injury of experimental chronic renal failure. Kidney Int 1996;50(suppl.57):132-6.
  • Pollock DM, Divish BJ, Polakowski JS, Oppgenorth TJ Angiotensin II receptor blockade improves renal function in rats with reduced renal mass. J Farmachol Exp Ther 1993;267:657-63.
  • Remuzzi A., Perico N., Amuchastegui CS et al. Short- and long-term effect of angiotensin II receptor blockade in rats with experimental diabetes. J Am Soc Nephrol 1993;4:40-9.[Abstract]
  • Lee DY, Kim W., Kang SK, Koh GY, Park SK Angiotensin-converting enzyme gene polymorphism in patients with minimal-change nephrotic syndrome and focal segmental glomerulosclerosis. Nephron 1997;77:471-3.[Web of Science][Medline] [Order article via Infotrieve]
  • Al-Eisa A., Haider MZ, Srivastva BS Angiotensin-converting enzyme gene insertion/deletion polymorphism in idiopathic nephrotic syndrome in Kuwaiti Arab children. Scand J Urol Nephrol 2001;35:239-42.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Harden PN, Geddes C., Rowe PA et al. Polymorphism in angiotensin converting enzyme gene and progression of IgA nephropathy. Lancet 1995;345:1540-2.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Marre M., Jeunmaitre X., Gallois Y. et al. Contribution of genetic polymorphism in the renin-angiotensin system to the development of renal complications in insulin-dependent diabetes. J Clin Invest 1997;99:1585-95.[Web of Science][Medline] [Order article via Infotrieve]
  • Hostteter TH, Olson JL, Rennke HG, Venkatachalam VA, Brenner BM Hiperfiltration in remnant nephrons: A potentially adverse response to renal ablation. Am J Physiol 1981;241:85-95.
  • Brenner BM Nephron adaptation to renal ablation and injury. Am J Physiol 1985;249:324-37.
  • Remuzzi G., Ruggenenti P., Benigni A. Pathophysiology of progressive nephropathy. Kidney Int 1997;51:2-15.[Web of Science][Medline] [Order article via Infotrieve]
  • Matsusaka T., Hymes J., Ichikawa I. Angiotensin in progressive renal disease: Theory and practice. J Am Soc Nephrol 1996;7:2025-43.[Abstract]

Journal of Renin-Angiotensin-Aldosterone System, Vol. 6, No. 3, 138-144 (2005)
DOI: 10.3317/jraas.2005.020
Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati   Add to Twitter Twitter    What's this?



This Article
Right arrow Abstract Freely available
Right arrow Free Full Text (Free PDF) Free
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to Saved Citations
Right arrow Download to citation manager
Right arrowRequest Permissions
Right arrow Request Reprints
Right arrow Add to My Marked Citations
Citing Articles
Right arrow Citing Articles via Google Scholar
Right arrow Citing Articles via Scopus
Google Scholar
Right arrow Articles by Tabel, Y.
Right arrow Articles by Ytlmaz, E.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Tabel, Y.
Right arrow Articles by Ytlmaz, E.
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati   Add to Twitter  
What's this?

Advertisement