Journal
JOURNAL OF HEPATOLOGY
Volume 47, Issue 2, Pages 203-211Publisher
ELSEVIER
DOI: 10.1016/j.jhep.2007.03.021
Keywords
HCV; fibrosis; toll-like receptor; genetic polymorphism; innate immunity
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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. 6.11/10; P = 0.034). The variant was also enriched in patients with no or little fibrosis compared to those with higher stages (12.60/o 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. (C) 2007 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.
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