title: Nucleotide-binding oligomerization domain containing 2 (NOD2) variants are genetic risk factors for death and spontaneous bacterial peritonitis in liver cirrhosis.
abstract: Spontaneous bacterial peritonitis (SBP), a severe complication in patients with advanced liver cirrhosis, has been attributed to bacterial translocation from the intestine. Variants of the NOD2 (nucleotide-binding oligomerization domain containing 2) gene have been associated with impaired mucosal barrier function in Crohn disease. We hypothesized that the risk of acquiring SBP is increased in patients with cirrhosis carrying NOD2 variants. We recruited 150 nonselected patients with liver cirrhosis and ascites admitted to our unit, monitored survival, and recorded the development of SBP prospectively and retrospectively. SBP was defined as the presence of polymorphonuclear neutrophil (PMN) cells >250 per microL of ascitic fluid. Patients were genotyped for the NOD2 variants p.R702W, p.G908R, and c.3020insC. During a median follow-up of 155 days, 54 patients (36%) died and SBP was diagnosed in 30 patients (20%). The occurrence of SBP was increased significantly (P = 0.008) in carriers of NOD2 variants (odds ratio [OR] = 3.06). Retrospectively, SBP was observed in 22 additional patients, and the combined prospective and retrospective analysis substantiated the association between NOD2 and SBP (P = 0.004; OR = 2.98). Of note, carriers of NOD2 risk alleles showed a significantly (P = 0.007) reduced mean survival time (274 days) in comparison to patients with wildtype genotypes (395 days).
  
  
  CONCLUSIONS
  Common NOD2 variants linked previously to impaired mucosal barrier function may be genetic risk factors for death and SBP. These findings might serve to identify patients with cirrhotic ascites eligible for preemptive antibiotic treatment.
authors.affiliation: Department of Internal Medicine I, University Hospital Bonn, University of Bonn, Bonn, Germany.
authors.forename: Beate
authors.initials: B
authors.lastname: Appenrodt
authors.forename: Frank
authors.initials: F
authors.lastname: Grünhage
authors.forename: Martin G
authors.initials: MG
authors.lastname: Gentemann
authors.forename: Lydia
authors.initials: L
authors.lastname: Thyssen
authors.forename: Tilman
authors.initials: T
authors.lastname: Sauerbruch
authors.forename: Frank
authors.initials: F
authors.lastname: Lammert
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001424:Bacterial Infections / Q000235:genetics*; D002648:Child; D005260:Female; D006801:Humans; D008103:Liver Cirrhosis / Q000150:complications* / Q000401:mortality; D008875:Middle Aged; D053473:Nod2 Signaling Adaptor Protein / Q000235:genetics*; D010538:Peritonitis / Q000235:genetics*; D011446:Prospective Studies; D012307:Risk Factors
chemical_list: C429018:NOD2 protein, human; D053473:Nod2 Signaling Adaptor Protein