A Toll-like receptor 7 single nucleotide polymorphism protects from advanced inflammation and fibrosis in male patients with chronic HCV-infection

J Hepatol. 2007 Aug;47(2):203-11. doi: 10.1016/j.jhep.2007.03.021. Epub 2007 Apr 12.


Background/aims: HCV-infection leads to development of liver fibrosis, causing morbidity and mortality. Multiple factors influence the progression of fibrosis, including genetic factors. Since HCV is an RNA virus, a role for TLR7 in the immune response against HCV is likely. No systematic analysis of TLR7 single nucleotide polymorphisms (SNPs) has been published.

Methods: We sequenced TLR7 in 52 women and investigated SNPs with an allele frequency >5% in 807 patients with chronic HCV-infection by melting curve analysis. We analyzed the effect of TLR7 SNPs on grade of inflammation and stage of fibrosis as determined by liver biopsy.

Results: We detected five TLR7 SNPs, three of which showed a frequency >5%. One variant, c.1-120T>G, was more common in patients with no or little inflammation than in patients with grades 2-4 (10.7% vs. 6.1%; P=0.034). The variant was also enriched in patients with no or little fibrosis compared to those with higher stages (12.6% vs. 6.6%; P=0.005). The difference was fully attributable to male patients.

Conclusions: This is the first analysis of TLR7 SNPs in patients with chronic HCV-infection. Our data suggest that the c.1-120G TLR7 allele offers protection from the development of inflammation and fibrosis in male patients with chronic HCV-infection.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Female
  • Gene Frequency
  • Genotype
  • Guanine
  • Hepatitis C, Chronic / complications*
  • Hepatitis C, Chronic / genetics*
  • Humans
  • Liver Cirrhosis / pathology*
  • Liver Cirrhosis / virology*
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide*
  • Severity of Illness Index
  • Sex Factors*
  • Thymine
  • Toll-Like Receptor 7 / genetics*


  • TLR7 protein, human
  • Toll-Like Receptor 7
  • Guanine
  • Thymine