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NDT Advance Access published online on April 6, 2009

Nephrology Dialysis Transplantation, doi:10.1093/ndt/gfp161
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© The Author [2009]. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved. For Permissions, please e-mail: journals.permissions@oxfordjournals.org



The impact of eNOS, MTR and MTHFR polymorphisms on renal graft survival in children and young adults

Lina Artifoni1, Elisa Benetti2, Sonia Centi1, Susanna Negrisolo1, Gian Marco Ghiggeri3, Fabrizio Ginevri3, Luciana Ghio4, Alberto Edefonti4, Caterina Brambilla5, Nicoletta Cagni5 and Luisa Murer2,1

1 Laboratory of Paediatric Nephrology 2 Paediatric Nephrology, Dialysis and Transplantation Unit, Department of Paediatrics, University of Padua, Padua 3 Laboratory of Pathophysiology of Uremia, Istituto Giannina Gaslini, Genoa 4 Paediatric Renal Unit G. e D. de Marchi, Fondazione Policlinico, Mangiagalli, Regina Elena 5 Transplant Immunology, Ospedale Maggiore Policlinico, Mangiagalli, Regina Elena, Milan, Italy

Correspondence and offprint requests to: Lina Artifoni; E-mail: lina.artifoni{at}unipd.it



  Abstract

Background. The main cause of reduced long-term graft survival is chronic allograft injury. Cardiovascular risk factors such as hyperhomocysteinaemia, accumulation of asymmetric dimethylarginine, increased oxidative stress and decreased production of nitric oxide seem to play an important role. Functional polymorphisms of the endothelial isoform of nitric oxide synthase (NOS) gene cause an alteration in nitric oxide production. Nitric oxide levels, and thus oxidative stress, are also influenced by hyperhomocysteinaemia.

Methods. We carried out a genetic analysis of endothelial nitric oxide synthase (eNOS) 894G>T, methionine synthase (MTR) 2756A>G and methylenetetrahydrofolate reductase (MTHFR) 677C>T/1298A>C in 268 renal allograft recipient/donor (D/R) matches, with respect to long-term graft survival.

Results. While MTHFR 677C>T/1298A>G and MTR 2756A>G polymorphism distribution in both recipients (R) and donors (D) showed no significant difference between matches with loss of graft function and those with long-term graft survival, the frequency of the eNOS 894TT genotype of donors was significantly increased (P = 0.040) in matches with better graft survival. The multivariate analysis identified the eNOS 894 genotype and clinically acute rejection episodes as independent risk factors for graft loss (P = 0.0406 and P = 0.0093, respectively).

Conclusions. The association between eNOS 894G>T polymorphism of donors and graft survival seems to suggest a role for this gene in chronic allograft injury; however, further studies are needed to confirm this hypothesis.

Keywords: allograft nephropathy; graft survival; polymorphisms; renal transplantation

Received for publication: 15. 7.08
Accepted in revised form: 19. 3.09


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