Lutz Philipp, Krämer Benjamin, Kaczmarek Dominik J, Hübner Marc P, Langhans Bettina, Appenrodt Beate, Lammert Frank, Nattermann Jacob, Hoerauf Achim, Strassburg Christian P, Spengler Ulrich, Nischalke Hans Dieter
Department of Internal Medicine I, University of Bonn, Bonn, Germany; German Center for Infection Research, Germany.
Department of Internal Medicine I, University of Bonn, Bonn, Germany; German Center for Infection Research, Germany.
Dig Liver Dis. 2016 Jan;48(1):62-8. doi: 10.1016/j.dld.2015.09.011. Epub 2015 Sep 28.
Spontaneous bacterial peritonitis is frequently a fatal infection in patients with liver cirrhosis. We investigated if nuclear dot protein 52kDa (NDP52), a negative regulator of toll-like receptor (TLR) signalling and autophagy adaptor protein, might be involved.
Two cohorts comprising 152 (derivation cohort) and 198 patients (validation cohort) with decompensated liver cirrhosis and 168 healthy controls were genotyped for the rs2303015 polymorphism in the NDP52 gene and prospectively followed-up for spontaneous bacterial peritonitis.
Overall, 57 (38%) patients in the derivation cohort and 77 (39%) in the validation cohort had spontaneous bacterial peritonitis. Cirrhosis was due to alcohol abuse in 57% of the derivation and 66% of the validation cohort. In patients with alcoholic cirrhosis, patients with spontaneous bacterial peritonitis had an increased frequency of the NDP52 rs2303015 minor variant in the derivation (p=0.04) and in the validation cohort (p=0.01). Multivariate analysis confirmed this minor variant (odds ratio 4.7, p=0.002) and the TLR2 -16934 TT variant (odds ratio 2.5, p=0.008) as risk factors for spontaneous bacterial peritonitis. In addition, presence of the NDP52 minor variant affected survival negatively.
Presence of the NDP52 rs2303015 minor variant increases the risk for spontaneous bacterial peritonitis in patients with alcoholic cirrhosis.
自发性细菌性腹膜炎在肝硬化患者中常常是一种致命性感染。我们研究了Toll样受体（TLR）信号传导的负调节因子及自噬衔接蛋白核斑点蛋白52kDa（NDP52）是否与之有关。
对两个队列进行基因分型，其中一个队列包括152例失代偿期肝硬化患者（衍生队列），另一个队列包括198例患者（验证队列），同时纳入168名健康对照者，检测NDP52基因rs2303015多态性，并对自发性细菌性腹膜炎进行前瞻性随访。
总体而言，衍生队列中有57例（38%）患者、验证队列中有77例（39%）患者发生自发性细菌性腹膜炎。衍生队列中57%、验证队列中66%的肝硬化由酒精滥用所致。在酒精性肝硬化患者中，衍生队列（p=0.04）和验证队列（p=0.01）中发生自发性细菌性腹膜炎的患者NDP52 rs2303015次要变异的频率增加。多变量分析证实该次要变异（比值比4.7，p=0.002）和TLR2 -16934 TT变异（比值比2.5，p=0.008）是自发性细菌性腹膜炎的危险因素。此外，NDP52次要变异的存在对生存有负面影响。
NDP52 rs2303015次要变异的存在增加了酒精性肝硬化患者发生自发性细菌性腹膜炎的风险。
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