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 |
Language: |
English |
Submitter: |
Factscience Import |
Date Deposited: |
04 Oct 2013 15:07 |
Last Modified: |
01 Jun 2023 09:44 |
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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