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Petrásek, J.* ; Hubácek, J.A.* ; Stickel, F.* ; Sperl, J.S.* ; Berg, T.* ; Ruf, E.* ; Wichmann, H.-E. ; Pfeufer, A. ; Meitinger, T. ; Trunecka, P.* ; Spicák, J.* ; Jirsa, M.*

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

Clin. Chem. Lab. Med. 47, 398-404 (2009)
DOI PMC
Open Access Green möglich sobald Postprint bei der ZB eingereicht worden ist.
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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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter alcoholic; genetic; interleukin-1 beta; liver cirrhosis; polymorphism; tumor necrosis factor-alpha; necrosis-factor-alpha; promoter polymorphism; japanese patients; deficient mice; receptor gene; risk-factor; in-vitro; disease; injury; association
ISSN (print) / ISBN 1434-6621
e-ISSN 1437-4331
Zeitschrift Clinical Chemistry and Laboratory Medicine
Quellenangaben Band: 47, Heft: 4, Seiten: 398-404 Artikelnummer: , Supplement: ,
Verlag de Gruyter
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Human Genetics (IHG)
Institute of Epidemiology (EPI)