title: Inosine monophosphate dehydrogenase polymorphisms and renal allograft outcome.
abstract: BACKGROUND
  Interindividual variation in inosine monophosphate dehydrogenase (IMPDH) enzyme activity and adverse effects caused by mycophenolate mofetil (MMF) inhibition may be genetically determined, and if so, transplant recipients should receive personalized dosing regimens of MMF, which would maximize efficacy and minimize toxicity. Some studies have demonstrated a relationship between the single nucleotide polymorphism and the risk of acute rejection with IMPDH I variants rs2278293 and rs2278294 and IMPDH II variant rs11706052, whereas others have failed to exhibit an effect. The aim of this work was to investigate the influence of these polymorphisms on acute rejection rates, graft survival and function, and MMF doses in a large cohort of patients.
  
  
  METHODS
  A random sample of 1040 recipients from the Collaborative Transplant Study DNA bank was genotyped for the variants IMPDH I rs2278293 and rs2278294 and IMPDH II rs11706052.
  
  
  RESULTS
  The presence of the T (rs2278293) and G alleles (rs2278294) in the IMPDH I variants and carriage of the G allele (rs11706052) in the IMPDH II variant did not increase the risk of rejection or affect graft function by 1 year after transplantation. There was no association with MMF dose tolerated at 1 year. Furthermore, these polymorphisms did not impact graft or patient survival at 5 years.
  
  
  CONCLUSIONS
  This study represents the largest cohort of patients with the longest follow-up to date and does not support previous evidence for an association between these IMPDH variants and renal allograft rejection and graft survival.
authors.affiliation: Department of Translational Medicine and Therapeutics, Queen Mary University of London, Barts and the London School of Medicine and Dentistry, London, UK.
authors.forename: Sapna
authors.initials: S
authors.lastname: Shah
authors.forename: Steven M
authors.initials: SM
authors.lastname: Harwood
authors.forename: Bernd
authors.initials: B
authors.lastname: Döhler
authors.forename: Gerhard
authors.initials: G
authors.lastname: Opelz
authors.forename: Muhammad M
authors.initials: MM
authors.lastname: Yaqoob
mesh_terms: D018070:Biological Specimen Banks; D005787:Gene Frequency; D005838:Genotype; D006084:Graft Rejection / Q000201:enzymology / Q000235:genetics* / Q000276:immunology / Q000517:prevention & control; D006085:Graft Survival / Q000187:drug effects; D006801:Humans; D007168:IMP Dehydrogenase / Q000235:genetics*; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D053208:Kaplan-Meier Estimate; D016030:Kidney Transplantation / Q000009:adverse effects / Q000276:immunology; D015999:Multivariate Analysis; D009173:Mycophenolic Acid / Q000031:analogs & derivatives / Q000627:therapeutic use; D010641:Phenotype; D011110:Polymorphism, Genetic; D016016:Proportional Hazards Models; D018570:Risk Assessment; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D007166:Immunosuppressive Agents; D007168:IMP Dehydrogenase; D009173:Mycophenolic Acid