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

Petrásek, Jan; Hubácek, Jaroslav A; Stickel, Felix; Sperl, Jan; Berg, Thomas; Ruf, Esther; Wichmann, H-Erich; Pfeufer, Arne; Meitinger, Thomas; Trunecka, Pavel; Spicák, Julius; Jirsa, Milan (2009). Do common genetic variants in endotoxin signaling pathway contribute to predisposition to alcoholic liver cirrhosis? Clinical chemistry and laboratory medicine, 47(4), pp. 398-404. Berlin: Walter de Gruyter 10.1515/CCLM.2009.112

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BACKGROUND: Tumor necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta), 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-1beta, 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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Service Sector > Institute of Clinical Pharmacology and Visceral Research (discontinued)

UniBE Contributor:

Stickel, Felix

ISSN:

1434-6621

ISBN:

19278365

Publisher:

Walter de Gruyter

Submitter:

Factscience Import

Date Deposited:

04 Oct 2013 15:07

Last Modified:

27 Apr 2018 09:23

Publisher DOI:

10.1515/CCLM.2009.112

PubMed ID:

19278365

Web of Science ID:

000266014200004

BORIS DOI:

10.7892/boris.29577

URI:

https://boris.unibe.ch/id/eprint/29577 (FactScience: 146658)

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