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-kappaB 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.


METHODS
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.


CONCLUSIONS
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.
Brenmoehl
Julia
J
University Hospital of Regensburg, Department of Internal Medicine I, 93042 Regensburg, Germany.
Herfarth
Hans
H
Glück
Thomas
T
Audebert
Franz
F
Barlage
Stefan
S
Schmitz
Gerd
G
Froehlich
Dieter
D
Schreiber
Stefan
S
Hampe
Jochen
J
Schölmerich
Jürgen
J
Holler
Ernst
E
Rogler
Gerhard
G
D018806:APACHE; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D005838:Genotype; D006801:Humans; D007362:Intensive Care Units; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009154:Mutation; D053473:Nod2 Signaling Adaptor Protein / Q000235:genetics*; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D011659:Pulmonary Gas Exchange; D012307:Risk Factors; D018805:Sepsis / Q000401:mortality*
C429018:NOD2 protein, human; D053473:Nod2 Signaling Adaptor Protein