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

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

In: Intensive Care Medicine, 2007, vol. 33, no. 9, p. 1541-1548

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    Titre
    • Genetic variants in the NOD2/CARD15 gene are associated with early mortality in sepsis patients
    Auteur
    • Brenmoehl, Julia. Department of Internal Medicine I, University Hospital of Regensburg, 93042, Regensburg, Germany
    • Herfarth, Hans. Department of Internal Medicine I, University Hospital of Regensburg, 93042, Regensburg, Germany
    • Glück, Thomas. Department of Internal Medicine I, University Hospital of Regensburg, 93042, Regensburg, Germany
    • Audebert, Franz. Department of Internal Medicine I, University Hospital of Regensburg, 93042, Regensburg, Germany
    • Barlage, Stefan. Institute of Clinical Chemistry, University Hospital of Regensburg, 93042, Regensburg, Germany
    • Schmitz, Gerd. Institute of Clinical Chemistry, University Hospital of Regensburg, 93042, Regensburg, Germany
    • Froehlich, Dieter. Department of Anestesiology, University Hospital of Regensburg, 93042, Regensburg, Germany
    • Schreiber, Stefan. Institute for Clinical Molecular Biology, Christian-Albrechts University, Schittenhelmstrasse 12, 24105, Kiel, Germany
    • Hampe, Jochen. Institute for Clinical Molecular Biology, Christian-Albrechts University, Schittenhelmstrasse 12, 24105, Kiel, Germany
    • Schölmerich, Jürgen. Department of Internal Medicine I, University Hospital of Regensburg, 93042, Regensburg, Germany
    • Holler, Ernst. Division of Hematology/Oncology, University Hospital of Regensburg, 93042, Regensburg, Germany
    • Rogler, Gerhard. Department of Internal Medicine I, University Hospital of Regensburg, 93042, Regensburg, Germany
    Type de document
    • Postprint
    Identifiant OAI-PMH
    • oai:doc.rero.ch:312331
    Summary
    Objective: Genetic variants in the NOD2/CARD15 gene resulting in adiminished 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 asignificantly increased rate of transplant related mortality (TRM) due to intestinal and pulmonary complications in stem cell transplantation (SCT). To assess apossible 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 (day30) 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 amajor role of NOD2/CARD15 coding variants for SRM. This may be indicative for arole of impaired barrier function and bacterial translocation in the pathophysiology of early sepsis related death