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21 May 2009

Donor dependent genetic factors and the long-term renal graft function

M Krajewska, K Kościelska-Kasprzak, D Drulis-Fajdasz, W Weyde, K Madziarska, O Mazanowska, M Kusztal, M Klinger

Ann Transplant 2009; 14(1): 33-33 :: ID: 880318

Abstract

Background: The aim was an analysis of the relations between the genetic  features of fetuin A, homocysteine, PAI-1, MMP-9, MPO, eNOS, IL-1B, IL-6, CRP) in donors and the long-term graft function. The study was extended by an analysis of the impact of the donor's age, gender compatibility, CIT, DGF and the presence of vasculopathy.
Material/Methods: The observation of 125 kidney recipients lasted a min. of twelve months (30.9±13.0 months). Grafts were obtained from 89 donors. CIT was 22.7±6.5 h. AHSG 1/2, MMP9-1562 C/T, IL6-174G/C, IL1b 3954C/T, MTHFR 677C/T, MTHFR 1298A/C, NOS3-786C/T, and PAI1 4G/5G SNPs were determined with the use of SSP-PCR and MPO-463G/A and CRP-390C/T/A with RLFP analysis. NOS3 IV a/b VNTR polymorphism was genotyped through gel electrophoresis of the respective PCR-generated DNA fragment
Results: The presence of the genotype aa eNOS gene was associated with
worse twelve month graft function. The aa genotype was also linked with
acute rejection. The lowest values of GFR after twelve months were achieved by recipients who received a graft with homozygotic PAI1 gene 5G polymorphism, linking paradoxically with lower PAI-1 synthesis suggesting that the intensity of proteolysis leading to an increased alloantigen specificity may stimulate alloresponse. The graft function depended significantly on the donor age and an influence of gender matching was observed. A statistically significant dependence of glomerular fi ltration on DGF was shown. The analysis of histopathological changes confi rmed that the presence of  vasculopathy is a factor of poor prognosis.
Conclusions: The genetic features of the donor influence long-term graft function. Variant eNOS gene polymorphism, which had a functional effect in the form of decreased eNOS activity, was linked with worse remote graft function.  A similar negative impact occurred in the case of donor PAI1 polymorphism, with the functional consequence of lower gene product synthesis

Keywords: Kidney Transplantation

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Annals of Transplantation eISSN: 2329-0358
Annals of Transplantation eISSN: 2329-0358