Intensive Care Medicine

, Volume 33, Issue 9, pp 1541–1548

Genetic variants in the NOD2/CARD15 gene are associated with early mortality in sepsis patients

  • Julia Brenmoehl
  • Hans Herfarth
  • Thomas Glück
  • Franz Audebert
  • Stefan Barlage
  • Gerd Schmitz
  • Dieter Froehlich
  • Stefan Schreiber
  • Jochen Hampe
  • Jürgen Schölmerich
  • Ernst Holler
  • Gerhard Rogler
Original

DOI: 10.1007/s00134-007-0722-z

Cite this article as:
Brenmoehl, J., Herfarth, H., Glück, T. et al. Intensive Care Med (2007) 33: 1541. doi:10.1007/s00134-007-0722-z

Abstract

Objective

Genetic variants in the NOD2/CARD15 gene resulting in a diminished capacity to activate NF-κB 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.

Design and patients

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.

Conclusion

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.

Keywords

SepsisNOD2/CARD15SNPsGenetic risk factors

Supplementary material

134_2007_722_MOESM1_ESM.doc (34 kb)
Electronic Supplementary Material (DOC 34K)

Copyright information

© Springer-Verlag 2007

Authors and Affiliations

  • Julia Brenmoehl
    • 1
  • Hans Herfarth
    • 1
  • Thomas Glück
    • 1
  • Franz Audebert
    • 1
  • Stefan Barlage
    • 2
  • Gerd Schmitz
    • 2
  • Dieter Froehlich
    • 3
  • Stefan Schreiber
    • 5
  • Jochen Hampe
    • 5
  • Jürgen Schölmerich
    • 1
  • Ernst Holler
    • 4
  • Gerhard Rogler
    • 1
    • 6
  1. 1.Department of Internal Medicine IUniversity Hospital of RegensburgRegensburgGermany
  2. 2.Institute of Clinical ChemistryUniversity Hospital of RegensburgRegensburgGermany
  3. 3.Department of AnestesiologyUniversity Hospital of RegensburgRegensburgGermany
  4. 4.Division of Hematology/OncologyUniversity Hospital of RegensburgRegensburgGermany
  5. 5.Institute for Clinical Molecular BiologyChristian-Albrechts UniversityKielGermany
  6. 6.Department of Internal Medicine, Clinic of Gastroenterology and HepatologyUniversity of ZurichZurichSwitzerland