NDT Advance Access originally published online on December 29, 2005
Nephrology Dialysis Transplantation 2006 21(4):979-983; doi:10.1093/ndt/gfk012
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© The Author [2005]. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org
Original Articles: Dialysis and Transplantation
Genetic polymorphisms of the renin-angiotensin system in end-stage renal disease
1 Laboratory for Molecular Diagnostics of Multifactorial Diseases, 2 Department of Nephrology and 3 Department of Radiology, University Medical School, Lublin, Poland
Correspondence and offprint requests to: Monika Buraczynska, Laboratory for Molecular Diagnostics of Multifactorial Diseases, Department of Nephrology, University Medical School, Dr K. Jaczewskiego 8, 20-954 Lublin, Poland. Email: monika.buraczynska{at}am.lublin.pl
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
*MB and PK contributed equally to this paper.
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