title: Polymorphism of the TLR4 gene reduces the risk of hepatitis C virus-induced hepatocellular carcinoma.
abstract: OBJECTIVE
  Toll-like receptor 4 (TLR4) signalling participates in the innate immune response against hepatitis C virus (HCV) infection. TLR4 gene polymorphisms may influence the risk of HCV-induced hepatocellular carcinoma (HCC). This is a single-centre-based study designed to analyse the distribution of several TLR4 gene single nucleotide polymorphisms in healthy controls and in patients chronically infected with HCV, with and without HCC.
  
  
  METHODS
  We have determined three single nucleotide polymorphisms (rs2149356, rs4986791 and rs5030719) at the TLR4 gene in 155 patients with HCV-related HCC, 153 patients with chronic hepatitis C and 390 healthy controls. All were white and most were Spaniards.
  
  
  RESULTS
  (1) rs5030719 was monomorphic and was not further analysed; (2) the rs2149356 T allele carrier state was significantly less frequent in patients with HCC than in healthy controls (OR 0.421, 95% CI 0.285-0.625) and in patients with chronic hepatitis C (OR 0.426, 95% CI 0.236-0.767); (3) the proportion of rs2149356 T allele carriers progressively diminished with increasing clinical stage of HCC; (4) no significant differences were observed for the rs4986791 T allele.
  
  
  CONCLUSIONS
  The TLR4 rs2148356 T allele is associated with a reduced risk of HCC and could slow down its clinical progression in HCV-induced chronic liver disease.
authors.affiliation: Department of Pharmacology, Medical School, University of Extremadura, Badajoz, Spain.
authors.forename: José A
authors.initials: JA
authors.lastname: Agúndez
authors.forename: Elena
authors.initials: E
authors.lastname: García-Martín
authors.forename: María J
authors.initials: MJ
authors.lastname: Devesa
authors.forename: Miguel
authors.initials: M
authors.lastname: Carballo
authors.forename: Carmen
authors.initials: C
authors.lastname: Martínez
authors.forename: Anna
authors.initials: A
authors.lastname: Lee-Brunner
authors.forename: Cristina
authors.initials: C
authors.lastname: Fernández
authors.forename: Manuel
authors.initials: M
authors.lastname: Díaz-Rubio
authors.forename: José M
authors.initials: JM
authors.lastname: Ladero
mesh_terms: D000368:Aged; D000483:Alleles; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000821:virology*; D002908:Chronic Disease; D018450:Disease Progression; D005260:Female; D005838:Genotype; D006526:Hepatitis C / Q000150:complications / Q000235:genetics / Q000378:metabolism*; D006579:Heterozygote; D006801:Humans; D008107:Liver Diseases / Q000235:genetics; D008113:Liver Neoplasms / Q000235:genetics* / Q000821:virology*; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D013030:Spain; D051197:Toll-Like Receptor 4 / Q000235:genetics* / Q000502:physiology*
chemical_list: C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4