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Mouse Kidney Transplantation: Models of Allograft Rejection
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Mouse Kidney Transplantation: Models of Allograft Rejection

Published on: October 11, 2014

Inosine monophosphate dehydrogenase polymorphisms and renal allograft outcome

Sapna Shah1, Steven M Harwood, Bernd Döhler

  • 1Department of Translational Medicine and Therapeutics, Queen Mary University of London, Barts and the London School of Medicine and Dentistry, London, UK.

Transplantation
|September 11, 2012
PubMed
Abstract

Insights

Genetic variations in inosine monophosphate dehydrogenase (IMPDH) do not appear to influence kidney transplant rejection or graft survival. This large-scale study found no link between IMPDH gene polymorphisms and patient outcomes with mycophenolate mofetil (MMF) treatment.

Area of Science:

  • Pharmacogenomics
  • Transplantation immunology
  • Molecular genetics

Background:

  • Interindividual variation in inosine monophosphate dehydrogenase (IMPDH) activity may affect mycophenolate mofetil (MMF) efficacy and toxicity.
  • Genetic polymorphisms in IMPDH have been inconsistently linked to kidney transplant rejection.
  • Personalized MMF dosing based on IMPDH genotype is a potential strategy to improve transplant outcomes.

Purpose of the Study:

  • To investigate the influence of IMPDH I (rs2278293, rs2278294) and IMPDH II (rs11706052) polymorphisms on acute rejection rates.
  • To assess the impact of these IMPDH variants on graft survival, graft function, and MMF dosage.
  • To evaluate these associations in a large cohort of kidney transplant recipients with long-term follow-up.

Main Methods:

  • Genotyping of 1040 kidney transplant recipients for IMPDH I variants rs2278293 and rs2278294, and IMPDH II variant rs11706052.
  • Analysis of acute rejection rates, graft survival, graft function, and MMF doses at 1 and 5 years post-transplantation.
  • Utilizing DNA samples from the Collaborative Transplant Study DNA bank.

Main Results:

  • No increased risk of rejection or impaired graft function was observed with the T allele (rs2278293) or G allele (rs2278294) of IMPDH I, or the G allele (rs11706052) of IMPDH II.
  • No association was found between these IMPDH polymorphisms and the MMF dose tolerated at 1 year.
  • Graft and patient survival at 5 years were not impacted by the studied IMPDH variants.

Conclusions:

  • This study, the largest to date with the longest follow-up, does not support a link between the investigated IMPDH polymorphisms and renal allograft rejection.
  • The findings suggest that IMPDH genetic variants rs2278293, rs2278294, and rs11706052 do not significantly influence clinical outcomes in kidney transplant recipients treated with MMF.
  • Current evidence does not support routine genetic screening of these IMPDH variants for MMF personalized dosing in transplantation.

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