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
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Intensive care medicine
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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.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.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.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.