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Genetic variations in Toll-like receptors 7 and 8 modulate natural hepatitis C outcomes and liver disease progression

Liver International Aug 18, 2017

Fakhir FZ, et al. – The present study aimed at analyzing the association between TLR7 and TLR8 polymorphisms and the hepatitis C virus (HCV) infection outcomes in Moroccan subjects. As per findings, variations in TLR7 and TLR8 genes modulate the clearance and progression of HCV infection with different magnitudes between sexes. This thereby clarified the sex–specific differences observed regarding the susceptibility to chronic hepatitis.

Methods

  • A case–control study of 643 subjects was undertaken; 293 mild chronic hepatitis patients, 119 with advanced liver disease (AdLD), 93 with HCV spontaneous clearance and 138 healthy controls were genotyped using TaqMan SNPs assays.

Results

  • Patients carrying TLR7 rs179008–A allele indicated more frequent spontaneous virus clearance (P=0.0001 for women, and P<0.001 for men).
  • Besides, carriage of TLR7 rs179009–A allele seemed associated with a 2–fold increase of spontaneous viral clearance in female patients (P=0.0002), but not in men.
  • In addition, an increase in the risk of disease progression was evident among individuals carrying TLR7 rs179008–T and rs179009–G alleles (P<0.05). 
  • TLR8 rs3764880–G allele seemed associated with spontaneous HCV clearance in both sexes (P<0.0001) albeit with an apparently stronger association in males (OR=6.02 for men vs 2.2 for women).
  • In males, TLR8 rs3764879–C and TLR8 rs3764880–A alleles seemed to have significant association with AdLD status (P<0.05).

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