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

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• 作者：Philipp Lutz^a ; ^d ; ^{philipp.lutz@ukb.uni-bonn.de" class="auth_mail" title="E-mail the corresponding author} ; Benjamin Krä ; mer^a ; ^d ; Dominik J. Kaczmarek^a ; ^d ; Marc P. Hü ; bner^b ; ^d ; Bettina Langhans^a ; ^d ; Beate Appenrodt^c ; Frank Lammert^c ; Jacob Nattermann^a ; ^d ; Achim Hoerauf^b ; ^d ; Christian P. Strassburg^a ; ^d ; Ulrich Spengler^a ; ^d ; Hans Dieter Nischalke^a ; ^d
• 关键词：Ascites ; Autophagy ; NDP52 ; SBP ; rs2303015
• 刊名：Digestive and Liver Disease
• 出版年：2016
• 出版时间：January 2016
• 年：2016
• 卷：48
• 期：1
• 页码：62-68
• 全文大小：435 K

文摘

Spontaneous bacterial peritonitis is frequently a fatal infection in patients with liver cirrhosis. We investigated if nuclear dot protein 52 kDa (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.

Conclusion

Presence of the NDP52 rs2303015 minor variant increases the risk for spontaneous bacterial peritonitis in patients with alcoholic cirrhosis.