A variant in the nuclear dot protein 52kDa gene increases the risk for spontaneous bacterial peritonitis in patients with alcoholic liver cirrhosis.
BACKGROUND
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
Presence of the NDP52 rs2303015 minor variant increases the risk for spontaneous bacterial peritonitis in patients with alcoholic cirrhosis.
Department of Internal Medicine I, University of Bonn, Bonn, Germany; German Center for Infection Research, Germany. Electronic address: philipp.lutz@ukb.uni-bonn.de.
Philipp
P
Lutz
Department of Internal Medicine I, University of Bonn, Bonn, Germany; German Center for Infection Research, Germany.
Benjamin
B
Krämer
Department of Internal Medicine I, University of Bonn, Bonn, Germany; German Center for Infection Research, Germany.
Dominik J
DJ
Kaczmarek
Institute for Medical Microbiology, Immunology and Parasitology, University of Bonn, Bonn, Germany; German Center for Infection Research, Germany.
Marc P
MP
Hübner
Department of Internal Medicine I, University of Bonn, Bonn, Germany; German Center for Infection Research, Germany.
Bettina
B
Langhans
Department of Medicine II, Saarland University Medical Center, Saarland University, Homburg, Germany.
Beate
B
Appenrodt
Department of Medicine II, Saarland University Medical Center, Saarland University, Homburg, Germany.
Frank
F
Lammert
Department of Internal Medicine I, University of Bonn, Bonn, Germany; German Center for Infection Research, Germany.
Jacob
J
Nattermann
Institute for Medical Microbiology, Immunology and Parasitology, University of Bonn, Bonn, Germany; German Center for Infection Research, Germany.
Achim
A
Hoerauf
Department of Internal Medicine I, University of Bonn, Bonn, Germany; German Center for Infection Research, Germany.
Christian P
CP
Strassburg
Department of Internal Medicine I, University of Bonn, Bonn, Germany; German Center for Infection Research, Germany.
Ulrich
U
Spengler
Department of Internal Medicine I, University of Bonn, Bonn, Germany; German Center for Infection Research, Germany.
Hans Dieter
HD
Nischalke
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001201:Ascites / Q000209:etiology; D001424:Bacterial Infections / Q000150:complications*; D016022:Case-Control Studies; D018932:Chemokine CCL2 / Q000235:genetics; D005260:Female; D005838:Genotype; D006801:Humans; D008104:Liver Cirrhosis, Alcoholic / Q000150:complications*; D008297:Male; D008875:Middle Aged; D053473:Nod2 Signaling Adaptor Protein / Q000235:genetics; D009687:Nuclear Proteins / Q000235:genetics*; D010538:Peritonitis / Q000235:genetics* / Q000382:microbiology; D020641:Polymorphism, Single Nucleotide; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics; D012307:Risk Factors; D051195:Toll-Like Receptor 2 / Q000235:genetics; D055815:Young Adult; D000099150:Receptor, Farnesoid X-Activated
D018932:Chemokine CCL2; D053473:Nod2 Signaling Adaptor Protein; D009687:Nuclear Proteins; D018160:Receptors, Cytoplasmic and Nuclear; D051195:Toll-Like Receptor 2; D000099150:Receptor, Farnesoid X-Activated; C094297:CALCOCO2 protein, human; C111835:CCL2 protein, human; C429018:NOD2 protein, human; C495342:TLR2 protein, human
Ascites; Autophagy; NDP52; SBP; rs2303015