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

Eckart Schott; Heiko Witt; Konrad Neumann; Stefan Taube; Djin Y. Oh; Eckart Schreier; Sandra Vierich; Gero Puhl; Alexandra Bergk; Juliane Halangk; Viola Weich; Bertram Wiedenmann; Thomas Berg

doi:10.1016/j.jhep.2007.03.021

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

Eckart Schott, Heiko Witt, Konrad Neumann, Stefan Taube, Djin Y. Oh, Eckart Schreier, Sandra Vierich, Gero Puhl, Alexandra Bergk, Juliane Halangk, Viola Weich, Bertram Wiedenmann, Thomas Berg^*

^*Corresponding author for this work

85 Citations (Scopus)

Abstract

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.

Original language	English
Journal	Journal of Hepatology
Volume	47
Issue number	2
Pages (from-to)	203-211
Number of pages	9
ISSN	0168-8278
DOIs	https://doi.org/10.1016/j.jhep.2007.03.021
Publication status	Published - 01.08.2007

Funding

The authors thank Sascha Gille (TIB MOLBIOL, Berlin, Germany) for design of the FRET probes. This work was partially supported by an investigational grant from Anadys Pharmaceuticals, San Diego, CA, by the German Competence Network for Viral Hepatitis (Hep-Net) funded by the German Ministry of Education and Research (BMBF, 01 KI 0437, 01 KI 0402), by the EU-Vigilance network of excellence combating viral resistance (VIRGIL, LSHM-CT-2004-503359), by a Rahel-Hirsch award to DYO, and by the Sonnenfeld-Stiftung, Berlin, Germany (to HW).

Research Areas and Centers

Academic Focus: Center for Infection and Inflammation Research (ZIEL)

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.jhep.2007.03.021

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Schott, E., Witt, H., Neumann, K., Taube, S., Oh, D. Y., Schreier, E., Vierich, S., Puhl, G., Bergk, A., Halangk, J., Weich, V., Wiedenmann, B., & Berg, T. (2007). A Toll-like receptor 7 single nucleotide polymorphism protects from advanced inflammation and fibrosis in male patients with chronic HCV-infection. Journal of Hepatology, 47(2), 203-211. https://doi.org/10.1016/j.jhep.2007.03.021

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

abstract = "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.",

author = "Eckart Schott and Heiko Witt and Konrad Neumann and Stefan Taube and Oh, \{Djin Y.\} and Eckart Schreier and Sandra Vierich and Gero Puhl and Alexandra Bergk and Juliane Halangk and Viola Weich and Bertram Wiedenmann and Thomas Berg",

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Schott, E, Witt, H, Neumann, K, Taube, S, Oh, DY, Schreier, E, Vierich, S, Puhl, G, Bergk, A, Halangk, J, Weich, V, Wiedenmann, B & Berg, T 2007, 'A Toll-like receptor 7 single nucleotide polymorphism protects from advanced inflammation and fibrosis in male patients with chronic HCV-infection', Journal of Hepatology, vol. 47, no. 2, pp. 203-211. https://doi.org/10.1016/j.jhep.2007.03.021

TY - JOUR

T1 - A Toll-like receptor 7 single nucleotide polymorphism protects from advanced inflammation and fibrosis in male patients with chronic HCV-infection

AU - Schott, Eckart

AU - Witt, Heiko

AU - Neumann, Konrad

AU - Taube, Stefan

AU - Oh, Djin Y.

AU - Schreier, Eckart

AU - Vierich, Sandra

AU - Puhl, Gero

AU - Bergk, Alexandra

AU - Halangk, Juliane

AU - Weich, Viola

AU - Wiedenmann, Bertram

AU - Berg, Thomas

PY - 2007/8/1

Y1 - 2007/8/1

N2 - 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.

AB - 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.

UR - https://www.scopus.com/pages/publications/34347381278

U2 - 10.1016/j.jhep.2007.03.021

DO - 10.1016/j.jhep.2007.03.021

M3 - Journal articles

C2 - 17512627

AN - SCOPUS:34347381278

SN - 0168-8278

VL - 47

SP - 203

EP - 211

JO - Journal of Hepatology

JF - Journal of Hepatology

IS - 2

ER -

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

Abstract

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