Header

UZH-Logo

Maintenance Infos

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 (2007). Genetic variants in the NOD2/CARD15 gene are associated with early mortality in sepsis patients. Intensive Care Medicine, 33(9):1541-1548.

Abstract

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

Abstract

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

Statistics

Citations

Dimensions.ai Metrics
54 citations in Web of Science®
54 citations in Scopus®
Google Scholar™

Altmetrics

Downloads

34 downloads since deposited on 03 Jul 2019
17 downloads since 12 months
Detailed statistics

Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:National licences > 142-005
Dewey Decimal Classification:610 Medicine & health
Scopus Subject Areas:Health Sciences > Critical Care and Intensive Care Medicine
Language:English
Date:22 August 2007
Deposited On:03 Jul 2019 13:27
Last Modified:15 Apr 2021 14:54
Publisher:Springer
ISSN:0342-4642
OA Status:Green
Publisher DOI:https://doi.org/10.1007/s00134-007-0722-z
PubMed ID:17558494

Download

Green Open Access

Download PDF  'Genetic variants in the NOD2/CARD15 gene are associated with early mortality in sepsis patients'.
Preview
Content: Published Version
Language: English
Filetype: PDF (Nationallizenz 142-005)
Size: 158kB
View at publisher