Genetic variants in the NOD2/CARD15 gene are associated with early mortality in sepsis patients
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- Brenmoehl, J., Herfarth, H., Glück, T. et al. Intensive Care Med (2007) 33: 1541. doi:10.1007/s00134-007-0722-z
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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.
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.