PMID- 23009036
OWN - NLM
STAT- MEDLINE
DCOM- 20131125
LR  - 20171116
IS  - 1530-0277 (Electronic)
IS  - 0145-6008 (Linking)
VI  - 37
IP  - 2
DP  - 2013 Feb
TI  - Polymorphisms of the CD14 genes are associated with susceptibility to alcoholic 
      liver disease in Greek patients.
PG  - 244-51
LID - 10.1111/j.1530-0277.2012.01925.x [doi]
AB  - BACKGROUND: The incidence and severity of alcoholic liver disease (ALD) in 
      chronic drinkers has been found to correlate with some environmental factors and 
      especially with the dose of alcohol consumption, but it is obvious that other 
      parameters clearly contribute to individual alcohol susceptibility. Chronic 
      ethanol exposure leads to continuous endotoxin-mediated Toll-like receptor-4 
      (TLR-4) and CD14 activation and subsequent cytokine release resulting in chronic 
      inflammation with continued hepatocellular damage. Therefore, genetic studies of 
      polymorphism in TLR-4 and CD14 genes seem to be appropriate in determining 
      genetic susceptibility to ALD. Our aim is to evaluate in a series of Greek 
      drinkers, the possible association of polymorphisms in the TLR-4 and CD14 genes 
      with ALD. METHODS: In 96 patients with ALD polymorphism of TLR-4 and CD14 genes 
      were studied compared with 104 patients with cirrhosis of other etiology, 100 
      healthy subjects, and 50 patients with a history of alcohol abuse but without 
      liver disease. RESULTS: No association between ALD and the presence of the 
      Asp299Gly and Thr399Ile polymorphisms in the TLR-4 gene could be documented in 
      our patients. Regarding the CD14 -159 (C/T) genotypes, TT genotype and T allele 
      were found to be overrepresented in alcoholic patients compared with patients 
      with nonalcohol-induced liver disease and healthy controls. On the other side, 
      when compared patients with ALD and patients with alcohol abuse and no liver 
      disease, TT genotype was found to be significantly less frequent. There is no 
      statistically significant association with the presence of the T allele and the 
      severity of ALD, suggesting that CD14 polymorphism does not influence disease 
      severity in advanced stages of the disease. CONCLUSIONS: In our series in Greek 
      patients with alcohol abuse and alcoholic cirrhosis, a significant negative 
      association with the CD14 endotoxin receptor gene polymorphism (TT genotype) but 
      not with the TLR-4 gene polymorphism was documented.
CI  - Copyright (c) 2012 by the Research Society on Alcoholism.
FAU - Nezi, Vasiliki
AU  - Nezi V
AD  - Second Department of Internal Medicine , Hippokration General Hospital, 
      University of Athens Medical School, Athens, Greece. vnezi@otenet.gr
FAU - Deutsch, Melanie
AU  - Deutsch M
FAU - Gazouli, Maria
AU  - Gazouli M
FAU - Alexopoulou, Alexandra
AU  - Alexopoulou A
FAU - Paparrigopoulos, Thomas
AU  - Paparrigopoulos T
FAU - Liappas, Ioannis A
AU  - Liappas IA
FAU - Dourakis, Spyros P
AU  - Dourakis SP
LA  - eng
PT  - Journal Article
DEP - 20120925
PL  - England
TA  - Alcohol Clin Exp Res
JT  - Alcoholism, clinical and experimental research
JID - 7707242
RN  - 0 (Lipopolysaccharide Receptors)
RN  - 0 (TLR4 protein, human)
RN  - 0 (Toll-Like Receptor 4)
SB  - IM
MH  - Alcoholism/genetics
MH  - Alleles
MH  - Case-Control Studies
MH  - Female
MH  - Genetic Association Studies
MH  - Genetic Predisposition to Disease/*genetics
MH  - Genotype
MH  - Greece
MH  - Humans
MH  - Lipopolysaccharide Receptors/*genetics
MH  - Liver Cirrhosis, Alcoholic/genetics
MH  - Liver Diseases, Alcoholic/*genetics
MH  - Male
MH  - Middle Aged
MH  - Polymorphism, Single Nucleotide/*genetics
MH  - Toll-Like Receptor 4/*genetics
EDAT- 2012/09/27 06:00
MHDA- 2013/12/16 06:00
CRDT- 2012/09/27 06:00
PHST- 2012/03/19 00:00 [received]
PHST- 2012/07/06 00:00 [accepted]
PHST- 2012/09/27 06:00 [entrez]
PHST- 2012/09/27 06:00 [pubmed]
PHST- 2013/12/16 06:00 [medline]
AID - 10.1111/j.1530-0277.2012.01925.x [doi]
PST - ppublish
SO  - Alcohol Clin Exp Res. 2013 Feb;37(2):244-51. doi: 
      10.1111/j.1530-0277.2012.01925.x. Epub 2012 Sep 25.