Journal Article

Genetic polymorphisms of the renin-angiotensin system in end-stage renal disease

Monika Buraczynska, Piotr Ksiazek, Andrzej Drop, Wojciech Zaluska, Danuta Spasiewicz and Andrzej Ksiazek

in Nephrology Dialysis Transplantation

Published on behalf of European Renal Association - European Dialysis and Transplant Assoc

Volume 21, issue 4, pages 979-983
Published in print April 2006 | ISSN: 0931-0509
Published online December 2005 | e-ISSN: 1460-2385 | DOI: http://dx.doi.org/10.1093/ndt/gfk012
Genetic polymorphisms of the renin-angiotensin system in end-stage renal disease

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Background. End-stage renal disease (ESRD) is a complex phenotype resulting from underlying kidney diseases of different etiologies as well as from environmental and genetic factors. The responsible genes influencing the development and rate of progression to ESRD have yet to be defined. We examined an association of the three renin-angiotensin system (RAS) gene polymorphisms with renal disease and progression to ESRD in dialyzed patients.

Methods. Genotyping was performed in 745 ESRD patients and 520 control subjects for the angiotensin-converting enzyme (ACE) I/D, angiotensinogen (AGT) M235T and angiotensin II type 1 receptor (AT1R) A1166C gene polymorphisms using polymerase chain reaction and gel analysis.

Results. Allele and genotype frequencies of the ACE polymorphism did not differ significantly between ESRD patients and controls. The patient group showed an increased frequency of the T allele of the AGT polymorphism (P = 0.02) and the C allele and CC genotype of the AT1R polymorphism (P<0.01). There was an association of the AT1R gene polymorphism with the progression of renal disease to end-stage failure. The time from diagnosis to the onset of ESRD was significantly shorter in patients carrying the C allele than in subjects with the homozygous AA genotype (4.7 years vs 12.6 years, P<0.001). The observed effect was not associated with hypertension in studied subjects.

Conclusion. The results of our study demonstrate the association between the AT1R A/C polymorphism and renal disease progression. The CC/AC genotype of this polymorphism might serve as a predictor for early ESRD and might be useful in planning therapeutic strategies for individual patients.

Keywords: angiotensin-converting enzyme; angiotensinogen; angiotensin II type 1 receptor; DNA polymorphisms; end-stage renal disease

Journal Article.  3511 words.  Illustrated.

Subjects: Nephrology

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