NDT Advance Access published online on December 29, 2005
Nephrology Dialysis Transplantation, doi:10.1093/ndt/gfk012
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1 Laboratory for Molecular Diagnostics of Multifactorial Diseases, University Medical School, Lublin, Poland; Department of Nephrology, University Medical School, Lublin, Poland; MB and PK contributed equally to this paper
* To whom correspondence should be addressed. 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.
Received March 25, 2005
Accepted November 29, 2005
Original Article
Genetic polymorphisms of the renin-angiotensin system in end-stage renal disease
Monika Buraczynska 1 *,
Piotr Ksiazek 2,
Andrzej Drop 3,
Wojciech Zaluska 4,
Danuta Spasiewicz 5,
and
Andrzej Ksiazek 4
2 Laboratory for Molecular Diagnostics of Multifactorial Diseases, University Medical School, Lublin, Poland; MB and PK contributed equally to this paper
3 Department of Radiology, University Medical School, Lublin, Poland
4 Department of Nephrology, University Medical School, Lublin, Poland
5 Laboratory for Molecular Diagnostics of Multifactorial Diseases, University Medical School, Lublin, Poland
Monika Buraczynska, E-mail: monika.buraczynska{at}am.lublin.pl
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