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

Petrášek, Jan ; Hubáček, Jaroslav A. ; Stickel, Felix ; Šperl, Jan ; Berg, Thomas ; Ruf, Esther ; Wichmann, H.-Erich ; Pfeufer, Arne ; Meitinger, Thomas ; Trunečka, Pavel ; Špičák, Julius ; Jirsa, Milan

In: Clinical Chemistry and Laboratory Medicine, 2009, vol. 47, no. 4, p. 398-404

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    Titel
    • Do common genetic variants in endotoxin signaling pathway contribute to predisposition to alcoholic liver cirrhosis?
    Autor
    • Petrášek, Jan
    • Hubáček, Jaroslav A.. Institute for Clinical and Experimental Medicine, Prague, Czech Republic
    • Stickel, Felix. Institute of Clinical Pharmacology, Inselspital Bern, University of Bern, Switzerland
    • Šperl, Jan. Institute for Clinical and Experimental Medicine, Prague, Czech Republic
    • Berg, Thomas. Department of Medicine, Charité - Campus Virchow, Humboldt University Berlin, Berlin, Germany
    • Ruf, Esther. Helmholtz Center Munich, Munich, Germany
    • Wichmann, H.-Erich
    • Pfeufer, Arne
    • Meitinger, Thomas
    • Trunečka, Pavel. Institute for Clinical and Experimental Medicine, Prague, Czech Republic
    • Špičák, Julius. Institute for Clinical and Experimental Medicine, Prague, Czech Republic
    • Jirsa, Milan. Institute for Clinical and Experimental Medicine, Prague, Czech Republic
    Dokumententyp
    • Postprint
    Sprache
    • Englisch
    Veröffentlicht in
    • Clinical Chemistry and Laboratory Medicine, 2009, vol. 47, no. 4, p. 398-404. Walter de Gruyter
    Andere elektronische Ausgabe
    OAI-PMH-ID
    • oai:doc.rero.ch:298267
    Summary
    Background: Tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β), 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-α and IL-1β, 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. Clin Chem Lab Med 2009;47:398-404