Do common genetic variants in endotoxin signaling pathway contribute to predisposition to alcoholic liver cirrhosis?

Abstract

Background: Tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 beta (IL-1b), produced by endotoxin-activated Kupffer cells, play a key role in the pathogenesis of alcoholic liver cirrhosis (ALC). Alleles TNFA-238A, IL1B-31T and variant IL1RN*2 of repeat polymorphism in the gene encoding the IL-1 receptor antagonist increase production of TNF-alpha and IL-1b, respectively. Alleles CD14-159T, TLR4 c.896G and TLR4 c.1196T modify activation of Kupffer cells by endotoxin. We confirmed the published associations between these common variants and genetic predisposition to ALC by means of a large case-control association study conducted on two Central European populations. Methods: The study population comprised a Czech sample of 198 ALC patients and 370 controls (MONICA project), and a German sample of 173 ALC patients and 331 controls (KORA-Augsburg), and 109 heavy drinkers without liver disease. Results: Single locus analysis revealed no significant difference between patients and controls in all tested loci. Diplotype [IL1RN*2/*2; IL1B-31T+] was associated with increased risk of ALC in the pilot study, but not in the validation samples. Conclusions: Although cytokine mediated immune reactions play a role in the pathogenesis of ALC, hereditary susceptibility caused by variants in the corresponding genes is low in Central European populations

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Last time updated on 09/07/2019

This paper was published in PuSH.

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