title: NOD2 gene variants are a risk factor for culture-positive spontaneous bacterial peritonitis and monomicrobial bacterascites in cirrhosis.
abstract: BACKGROUND
  Spontaneous bacterial peritonitis (SBP) is considered as result of bacterial translocation from the gastrointestinal lumen to the mesenteric lymph nodes and subsequent circulation. Variants of the NOD2 gene contribute to bacterial translocation and were associated with SBP in a recent study.
  
  
  METHODS
  We determined common NOD2 variants by TaqMan polymerase chain reaction and analysed the ascitic fluid neutrophil count and bacterial culture results in 175 prospectively characterized hospitalized patients with decompensated cirrhosis who underwent diagnostic paracentesis in two German centres.
  
  
  RESULTS
  Ten patients presented with culture-positive SBP, 19 with culture-negative SBP and six had bacterascites. Minor allele frequencies for R702W, G908R and 1007fs in subjects with sterile non-neutrocytic ascites were 3.2, 2.5 and 2.5% respectively. Patients with SBP [odds ratio (OR) 2.7; P=0.036], culture-positive SBP (OR 6.0; P=0.012) and bacterascites (OR 6.0; P=0.050) were more often carriers of NOD2 variants than patients with sterile non-neutrocytic ascites. The mutations 1007fs and G908R were associated with culture-positive SBP (P ≤ 0.005) and R702W with bacterascites (P=0.014). There was no significant association of NOD2 variants with culture-negative SBP (OR 1.6; P=0.493). In logistic regression, previous SBP, a higher model for end-stage liver disease (MELD) score and the presence of a NOD2 variant were independent predictors of ascitic fluid infection. The median survival was insignificantly shorter in patients with NOD2 variants (268 vs. 339 days; P=0.386). In patients without hepatocellular carcinoma at study entry (N=148), NOD2 was a predictor of survival after adjustment for the MELD score and age (hazard ratio 1.89; P=0.045).
  
  
  CONCLUSIONS
  NOD2 variants increase the risk for culture-positive SBP and bacterascites in cirrhosis and may affect survival.
authors: Department of Internal Medicine II, Division of Gastroenterology, Hepatology, and Infectious Diseases, Jena University Hospital, Jena, Germany. t.bruns@bham.ac.uk
authors: Tony
authors: T
authors: Bruns
authors: Jack
authors: J
authors: Peter
authors: Philipp A
authors: PA
authors: Reuken
authors: Dominik H
authors: DH
authors: Grabe
authors: Sonja R
authors: SR
authors: Schuldes
authors: Julia
authors: J
authors: Brenmoehl
authors: Jürgen
authors: J
authors: Schölmerich
authors: Reiner
authors: R
authors: Wiest
authors: Andreas
authors: A
authors: Stallmach
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001201:Ascites / Q000235:genetics* / Q000382:microbiology / Q000401:mortality; D001202:Ascitic Fluid / Q000382:microbiology / Q000473:pathology; D001424:Bacterial Infections / Q000235:genetics* / Q000382:microbiology / Q000401:mortality; D018988:Bacterial Translocation; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005858:Germany / Q000453:epidemiology; D006801:Humans; D007958:Leukocyte Count; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000473:pathology; D053473:Nod2 Signaling Adaptor Protein / Q000235:genetics*; D010538:Peritonitis / Q000235:genetics* / Q000382:microbiology / Q000401:mortality; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D015996:Survival Rate
chemical_list: C429018:NOD2 protein, human; D053473:Nod2 Signaling Adaptor Protein