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

Authors:
Julia Brenmoehl, Hans Herfarth, Thomas Glück, Franz Audebert, Stefan Barlage, Gerd Schmitz, Dieter Froehlich, Stefan Schreiber, Jochen Hampe, Jürgen Schölmerich, Ernst Holler, Gerhard Rogler
Year of publication:
2007
Volume:
33
Issue:
9
Issn:
0342-4642
Journal title abbreviated:
INTENS CARE MED
Journal title long:
Intensive care medicine
Impact factor:
10.125
Abstract:
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.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.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.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.