title: Recipient's genetic R702W NOD2 variant is associated with an increased risk of bacterial infections after orthotopic liver transplantation.
abstract: BACKGROUND
  Orthotopic liver transplantation (OLT) is accompanied by a significant postoperative infection risk. Immunosuppression to prevent rejection increases the susceptibility to infections, mainly by impairing the adaptive immune system. Genetic polymorphisms in the lectin complement pathway of the donor have recently been identified as important risk determinants of clinically significant bacterial infection (CSI) after OLT. Another genetic factor involved in innate immunity is NOD2, which was reported to be associated with increased risk of spontaneous bacterial peritonitis in cirrhotic patients.
  
  
  METHODS
  We assessed association of three genetic NOD2 variants (R702W, G908R and 3020insC) with increased risk of CSI after OLT. 288 OLT recipient-donor pairs from two tertiary referral centers were genotyped for the three NOD2 variants. The probability of CSI in relation to NOD2 gene variants was determined with cumulative incidence curves and log-rank analysis.
  
  
  RESULTS
  The R702W NOD2 variant in the recipient was associated with CSI after OLT. Eight out of 15 (53.3%) individuals with a mutated genotype compared to 80/273 (29.3%) with wild type genotype developed CSI (p=0.027, univariate cox regression), illustrated by a higher frequency of CSI after OLT over time (p=0.0003, log rank analysis). Multivariate analysis (including the donor lectin complement pathway profile) showed independence of this R702W NOD2 association from other risk factors (HR 2.0; p=0.04). The other NOD2 variants, G908R and 3020insC, in the recipient were not associated with CSI. There was no association with CSI after OLT for any of the NOD2 variants in the donor.
  
  
  CONCLUSIONS
  The mutated NOD2 R702W genotype in the recipient is independently associated with an increased risk of bacterial infections after liver transplantation, indicating a predisposing role for this genetic factor impairing the recipient's innate immune system.
authors: Department of Gastroenterology and Hepatology, University of Groningen and University Medical Center Groningen, Groningen, The Netherlands.
authors: Marcel
authors: M
authors: Janse
authors: Bert-Jan F
authors: BJ
authors: de Rooij
authors: Bart
authors: B
authors: van Hoek
authors: Arie P
authors: AP
authors: van den Berg
authors: Robert J
authors: RJ
authors: Porte
authors: Hans
authors: H
authors: Blokzijl
authors: Minneke J
authors: MJ
authors: Coenraad
authors: Bouke G
authors: BG
authors: Hepkema
authors: Alexander F
authors: AF
authors: Schaapherder
authors: Jan
authors: J
authors: Ringers
authors: Rinse K
authors: RK
authors: Weersma
authors: Hein W
authors: HW
authors: Verspaget
mesh_terms: D000328:Adult; D001424:Bacterial Infections / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D016031:Liver Transplantation / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D053473:Nod2 Signaling Adaptor Protein / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012307:Risk Factors; D016019:Survival Analysis; D014019:Tissue Donors; D066027:Transplant Recipients
chemical_list: C429018:NOD2 protein, human; D053473:Nod2 Signaling Adaptor Protein
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