title: Genetic variants in the NOD2/CARD15 gene are associated with early mortality in sepsis patients.
abstract: OBJECTIVE
  Genetic variants in the NOD2/CARD15 gene resulting in a diminished capacity to activate NF-kappaB in response to bacterial cell wall products have been associated with Crohn's disease (CD). Recently, we found an association between the variant Leu1007fsinsC of the NOD2/CARD15 gene (SNP13) and a significantly increased rate of transplant related mortality (TRM) due to intestinal and pulmonary complications in stem cell transplantation (SCT). To assess a possible contribution of variants in the NOD2/CARD15 gene to sepsis related mortality (SRM) we investigated 132 prospectively characterised, consecutive patients with sepsis.
  
  
  METHODS
  The three most common NOD2/CARD15 variants (Arg702Trp, Gly908Arg, and Leu1007fsinsC) were determined in 132 prospectively characterised patients with sepsis attended to three intensive care units at the University of Regensburg by Taqman PCR. NOD2/CARD15 genotype and major patients' characteristics were correlated with SRM.
  
  
  RESULTS
  Patient groups with and without NOD2/CARD15 variants did not differ in their clinical characteristics such as median age, gender, reason for admission or APACHE score; however, SRM (day 30) was increased in patients with NOD2/CARD15 coding variants (42 vs. 31%) and was highest (57%) in 8 patients carrying the Leu1007fsinsC variant (p < 0.05). Multivariate analysis demonstrated the Leu1007fsinsC genetic variant as an independent risk factor for SRM.
  
  
  CONCLUSIONS
  Our findings indicate a major role of NOD2/CARD15 coding variants for SRM. This may be indicative for a role of impaired barrier function and bacterial translocation in the pathophysiology of early sepsis related death.
authors.affiliation: University Hospital of Regensburg, Department of Internal Medicine I, 93042 Regensburg, Germany.
authors.forename: Julia
authors.initials: J
authors.lastname: Brenmoehl
authors.forename: Hans
authors.initials: H
authors.lastname: Herfarth
authors.forename: Thomas
authors.initials: T
authors.lastname: Glück
authors.forename: Franz
authors.initials: F
authors.lastname: Audebert
authors.forename: Stefan
authors.initials: S
authors.lastname: Barlage
authors.forename: Gerd
authors.initials: G
authors.lastname: Schmitz
authors.forename: Dieter
authors.initials: D
authors.lastname: Froehlich
authors.forename: Stefan
authors.initials: S
authors.lastname: Schreiber
authors.forename: Jochen
authors.initials: J
authors.lastname: Hampe
authors.forename: Jürgen
authors.initials: J
authors.lastname: Schölmerich
authors.forename: Ernst
authors.initials: E
authors.lastname: Holler
authors.forename: Gerhard
authors.initials: G
authors.lastname: Rogler
mesh_terms: D018806:APACHE; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D005838:Genotype; D006801:Humans; D007362:Intensive Care Units; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009154:Mutation; D053473:Nod2 Signaling Adaptor Protein / Q000235:genetics*; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D011659:Pulmonary Gas Exchange; D012307:Risk Factors; D018805:Sepsis / Q000401:mortality*
chemical_list: C429018:NOD2 protein, human; D053473:Nod2 Signaling Adaptor Protein