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Clinical Chemistry and Laboratory Medicine (CCLM)

Published in Association with the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM)

Editor-in-Chief: Plebani, Mario

Ed. by Gillery, Philippe / Greaves, Ronda / Lackner, Karl J. / Lippi, Giuseppe / Melichar, Bohuslav / Payne, Deborah A. / Schlattmann, Peter


IMPACT FACTOR 2018: 3.638

CiteScore 2018: 2.44

SCImago Journal Rank (SJR) 2018: 1.191
Source Normalized Impact per Paper (SNIP) 2018: 1.205

Online
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1437-4331
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Volume 47, Issue 4

Issues

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

Jan Petrášek
  • Institute for Clinical and Experimental Medicine, Prague, Czech Republic
  • Current address: Department of Medicine, University of Massachusetts, Medical School, Worcester, MA, USA.
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Jaroslav A. Hubáček / Felix Stickel / Jan Šperl / Thomas Berg
  • Department of Medicine, Charité – Campus Virchow, Humboldt University Berlin, Berlin, Germany
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Esther Ruf / H.-Erich Wichmann / Arne Pfeufer
  • Helmholtz Center Munich, Munich, Germany
  • Technical University, Institute of Human Genetics, Munich, Germany
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Thomas Meitinger
  • Helmholtz Center Munich, Munich, Germany
  • Technical University, Institute of Human Genetics, Munich, Germany
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Pavel Trunečka / Julius Špičák / Milan Jirsa
Published Online: 2009-03-12 | DOI: https://doi.org/10.1515/CCLM.2009.112

Abstract

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.

Keywords: alcoholic; genetic; interleukin-1β; liver cirrhosis; polymorphism; tumor necrosis factor-α

About the article

Corresponding author: Jan Petrášek, MD, Laboratory of Experimental Hepatology, Institute for Clinical and Experimental Medicine, Vídeňská 1958, 14021, Praha 4, Czech Republic Phone: +420261362773, Fax: +420241721666,


Received: 2008-11-21

Accepted: 2009-01-20

Published Online: 2009-03-12

Published in Print: 2009-04-01


Citation Information: Clinical Chemistry and Laboratory Medicine, Volume 47, Issue 4, Pages 398–404, ISSN (Online) 1437-4331, ISSN (Print) 1434-6621, DOI: https://doi.org/10.1515/CCLM.2009.112.

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