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

Brenmoehl, Julia and Herfarth, Hans and Glueck, Thomas and Audebert, Franz and Barlage, Stefan and Schmitz, Gerd and Froehlich, Dieter and Schreiber, Stefan and Hampe, Jochen and Schoelmerich, Juergen and Holler, Ernst and Rogler, Gerhard (2007) Genetic variants in the NOD2/CARD15 gene are associated with early mortality in sepsis patients. INTENSIVE CARE MEDICINE, 33 (9). pp. 1541-1548. ISSN 0342-4642,

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Abstract

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.

Item Type: Article
Uncontrolled Keywords: INTENSIVE-CARE MEDICINE; KAPPA-B ACTIVATION; INTESTINAL EPITHELIAL-CELLS; INFLAMMATORY-BOWEL-DISEASE; APACHE-II; CROHNS-DISEASE; SEPTIC SHOCK; CONSENSUS CONFERENCE; ICU ORGANIZATION; INNATE IMMUNITY; sepsis; NOD2/CARD15; SNPs; genetic risk factors
Subjects: 600 Technology > 610 Medical sciences Medicine
Divisions: Medicine > Lehrstuhl für Innere Medizin I
Depositing User: Dr. Gernot Deinzer
Date Deposited: 01 Dec 2020 12:17
Last Modified: 01 Dec 2020 12:17
URI: https://pred.uni-regensburg.de/id/eprint/32285

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