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

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