title: A non-interventional study of the genetic polymorphisms of NOD2 associated with increased mortality in non-alcoholic liver transplant patients.
abstract: BACKGROUND
  Infections after liver transplantation are the main cause of death in the first year. Recent reports indicate that NOD2 gene mutations increase the risk for inflammatory bowl disease and the severity of graft-versus-host disease in bone marrow transplant patients. Data on polymorphisms in liver transplant patients are sparse. We analyzed 13 single-nucleotide polymorphisms (SNPs) of 13 different gene variants including the SNPs of NOD2 genes from liver recipients. The aim of the study was to evaluate the impact of the SNPs on dialysis-dependent kidney failure, the incidence of infections and patient survival.
  
  
  METHODS
  During a period of 20-months, 231 patients were recruited in this non-interventional, prospective study. Thirteen different SNPs and their impact on the patients' survival, infection rate, and use of dialysis were assessed.
  
  
  RESULTS
  NOD 2 wildtype genes were protective with respect to the survival of non-alcoholic, cirrhotic transplant patients (3 year survival: 66.8% wildtype vs. 42.6% gene mutation, p = 0.026). This effect was not observed in alcoholic transplant recipients.The incidence of dialysis-dependent kidney failure and infection in the liver transplant patients was not influenced by NOD 2 gene polymorphisms. No effect was noted in the remaining 12 SNPs.Patients with early allograft dysfunction experienced significantly more infections, required dialysis and had significantly worse survival.In contrast, the donor-risk-index had no impact on the infection rate, use of dialysis or survival.
  
  
  CONCLUSIONS
  NOD2 gene variants seem to play a key role in non-alcoholic, liver transplant recipients. However these data should be validated in a larger cohort.
authors.affiliation: Department of General- Visceral- and Transplant Surgery, University Duisburg-Essen, Hufelandstr 55, 45 122 Essen, Germany. fuat.saner@uni-due.de.
authors.forename: Fuat Hakan
authors.initials: FH
authors.lastname: Saner
authors.forename: Knut
authors.initials: K
authors.lastname: Nowak
authors.forename: Dieter
authors.initials: D
authors.lastname: Hoyer
authors.forename: Peter
authors.initials: P
authors.lastname: Rath
authors.forename: Ali
authors.initials: A
authors.lastname: Canbay
authors.forename: Andreas
authors.initials: A
authors.lastname: Paul
authors.forename: Michael
authors.initials: M
authors.lastname: Koldehoff
authors.forename: Ahmet
authors.initials: A
authors.lastname: Elmaağaclı
mesh_terms: D000328:Adult; D006801:Humans; D015994:Incidence; D007239:Infections / Q000453:epidemiology / Q000235:genetics*; D008104:Liver Cirrhosis, Alcoholic / Q000601:surgery; D016031:Liver Transplantation / Q000009:adverse effects / Q000401:mortality*; D008875:Middle Aged; D053473:Nod2 Signaling Adaptor Protein / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D006435:Renal Dialysis; D051437:Renal Insufficiency / Q000453:epidemiology / Q000235:genetics* / Q000628:therapy; D015996:Survival Rate
chemical_list: C429018:NOD2 protein, human; D053473:Nod2 Signaling Adaptor Protein