title: Polymorphisms of the CD14 genes are associated with susceptibility to alcoholic liver disease in Greek patients.
abstract: 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.
authors.affiliation: Second Department of Internal Medicine , Hippokration General Hospital, University of Athens Medical School, Athens, Greece. vnezi@otenet.gr
authors.forename: Vasiliki
authors.initials: V
authors.lastname: Nezi
authors.forename: Melanie
authors.initials: M
authors.lastname: Deutsch
authors.forename: Maria
authors.initials: M
authors.lastname: Gazouli
authors.forename: Alexandra
authors.initials: A
authors.lastname: Alexopoulou
authors.forename: Thomas
authors.initials: T
authors.lastname: Paparrigopoulos
authors.forename: Ioannis A
authors.initials: IA
authors.lastname: Liappas
authors.forename: Spyros P
authors.initials: SP
authors.lastname: Dourakis
mesh_terms: D000437:Alcoholism / Q000235:genetics; D000483:Alleles; D016022:Case-Control Studies; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006115:Greece; D006801:Humans; D018950:Lipopolysaccharide Receptors / Q000235:genetics*; D008104:Liver Cirrhosis, Alcoholic / Q000235:genetics; D008108:Liver Diseases, Alcoholic / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D051197:Toll-Like Receptor 4 / Q000235:genetics*
chemical_list: D018950:Lipopolysaccharide Receptors; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4