PMID- 19278365
OWN - NLM
STAT- MEDLINE
DCOM- 20090612
LR  - 20161018
IS  - 1434-6621 (Print)
IS  - 1434-6621 (Linking)
VI  - 47
IP  - 4
DP  - 2009
TI  - Do common genetic variants in endotoxin signaling pathway contribute to 
      predisposition to alcoholic liver cirrhosis?
PG  - 398-404
LID - 10.1515/CCLM.2009.112 [doi]
AB  - 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.
FAU - Petrasek, Jan
AU  - Petrasek J
AD  - Institute for Clinical and Experimental Medicine, Prague, Czech Republic. 
      jan.petrasek@ikem.cz
FAU - Hubacek, Jaroslav A
AU  - Hubacek JA
FAU - Stickel, Felix
AU  - Stickel F
FAU - Sperl, Jan
AU  - Sperl J
FAU - Berg, Thomas
AU  - Berg T
FAU - Ruf, Esther
AU  - Ruf E
FAU - Wichmann, H-Erich
AU  - Wichmann HE
FAU - Pfeufer, Arne
AU  - Pfeufer A
FAU - Meitinger, Thomas
AU  - Meitinger T
FAU - Trunecka, Pavel
AU  - Trunecka P
FAU - Spicak, Julius
AU  - Spicak J
FAU - Jirsa, Milan
AU  - Jirsa M
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Germany
TA  - Clin Chem Lab Med
JT  - Clinical chemistry and laboratory medicine
JID - 9806306
RN  - 0 (Endotoxins)
SB  - IM
MH  - Case-Control Studies
MH  - Endotoxins/*genetics/metabolism
MH  - Female
MH  - Genetic Predisposition to Disease/*genetics
MH  - Genetic Variation/*genetics
MH  - Genotype
MH  - Health
MH  - Humans
MH  - Liver Cirrhosis, Alcoholic/*genetics/metabolism
MH  - Male
MH  - *Signal Transduction
EDAT- 2009/03/13 09:00
MHDA- 2009/06/13 09:00
CRDT- 2009/03/13 09:00
PHST- 2009/03/13 09:00 [entrez]
PHST- 2009/03/13 09:00 [pubmed]
PHST- 2009/06/13 09:00 [medline]
AID - 10.1515/CCLM.2009.112 [doi]
PST - ppublish
SO  - Clin Chem Lab Med. 2009;47(4):398-404. doi: 10.1515/CCLM.2009.112.