Brenmoehl Julia, Herfarth Hans, Glück Thomas, Audebert Franz, Barlage Stefan, Schmitz Gerd, Froehlich Dieter, Schreiber Stefan, Hampe Jochen, Schölmerich Jürgen, Holler Ernst, Rogler Gerhard
University Hospital of Regensburg, Department of Internal Medicine I, 93042 Regensburg, Germany.
Intensive Care Med. 2007 Sep;33(9):1541-8. doi: 10.1007/s00134-007-0722-z. Epub 2007 Jun 9.
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.
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.
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.
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.
NOD2/CARD15基因中的遗传变异导致对细菌细胞壁产物激活NF-κB的能力减弱，这与克罗恩病（CD）相关。最近，我们发现NOD2/CARD15基因的Leu1007fsinsC变异（SNP13）与干细胞移植（SCT）中因肠道和肺部并发症导致的移植相关死亡率（TRM）显著增加有关。为了评估NOD2/CARD15基因变异对脓毒症相关死亡率（SRM）的可能影响，我们对132例经前瞻性特征分析的连续性脓毒症患者进行了研究。
通过Taqman PCR在雷根斯堡大学三个重症监护病房的132例经前瞻性特征分析的脓毒症患者中检测了三种最常见的NOD2/CARD15变异（Arg702Trp、Gly908Arg和Leu1007fsinsC）。NOD2/CARD15基因型与主要患者特征与SRM相关。
有和没有NOD2/CARD15变异的患者组在临床特征如年龄中位数、性别、入院原因或急性生理学及慢性健康状况评分系统（APACHE）评分方面没有差异；然而，携带NOD2/CARD15编码变异的患者30天SRM升高（42%对31%），在8例携带Leu1007fsinsC变异的患者中最高（57%）（p<0.05）。多变量分析表明Leu1007fsinsC基因变异是SRM的独立危险因素。
我们的研究结果表明NOD2/CARD15编码变异在SRM中起主要作用。这可能表明屏障功能受损和细菌易位在早期脓毒症相关死亡的病理生理学中起作用。
