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.
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.
Authors: Linda Grillová; Jana Musilová; Klára Janečková; Petra Pospíšilová; Ivana Kuklová; Vladana Woznicová; Hana Zákoucká; David Šmajs Journal: Infect Immun Date: 2020-12-15 Impact factor: 3.441
Authors: Jinsheng Guo; Feng Hong; Johnny Loke; Steven Yea; Chooi Ling Lim; Ursula Lee; Derek A Mann; Martin J Walsh; John J Sninsky; Scott L Friedman Journal: J Biol Chem Date: 2009-12-17 Impact factor: 5.157
Authors: Robert M Clancy; David Alvarez; Elena Komissarova; Franck J Barrat; Jordan Swartz; Jill P Buyon Journal: J Immunol Date: 2010-01-20 Impact factor: 5.422