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Epigenetic analysis of the IFNλ3 gene identifies a novel marker for response to therapy in HCV-infected subjects

Overview of attention for article published in Journal of Viral Hepatitis, December 2016
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Title
Epigenetic analysis of the IFNλ3 gene identifies a novel marker for response to therapy in HCV-infected subjects
Published in
Journal of Viral Hepatitis, December 2016
DOI 10.1111/jvh.12661
Pubmed ID
Authors

J. F. Waring, J. W. Davis, E. Dumas, D. Cohen, K. Idler, S. Abel, R. Georgantas, T. Podsadecki, S. Dutta

Abstract

Chronic hepatitis C virus (HCV) infection is characterized by high interindividual variability in response to pegylated interferon and ribavirin. A genetic polymorphism on chromosome 19 (rs12979860) upstream of interferon-λ3 (IFNλ3) is associated with a twofold change in sustained virologic response rate after 48 weeks of treatment with pegylated interferon/ribavirin in HCV genotype 1 (GT1) treatment-naïve patients. We conducted epigenetic analysis on the IFNλ3 promoter to investigate whether DNA methylation is associated with response to HCV therapy. DNA samples from HCV GT1-infected subjects receiving an interferon-free paritaprevir-containing combination regimen (N=540) and from HCV-uninfected, healthy controls (N=124) were analysed for IFNλ3 methylation levels. Methylation was strongly associated with rs12979860 allele status whether adjusting for HCV status (r=65.0%, 95% CI: [60.2%, 69.5%]), or not (r=64.4%), both with P<2.2×10(-16) . In HCV GT1-infected subjects, C/C genotypes had significantly lower methylation levels relative to C/T or T/T genotypes (P<1×10(-14) ), with each T allele resulting in a nine-unit increase in mean methylation level. Methylation levels did not correlate with response in subjects treated for 12 or 24 weeks. However, non-C/C subjects with higher methylation levels were more likely to relapse when treatment duration was 8 weeks. This analysis suggests that methylation status of the IFNλ3 promoter region may be a useful parameter that identifies patients more likely to relapse following HCV therapy; however, continuing therapy for a sufficient duration can overcome this difference. These findings may provide mechanistic insight into the role of IFNλ3 genetic variants in HCV treatment response.

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Mendeley readers

The data shown below were compiled from readership statistics for 5 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 5 100%

Demographic breakdown

Readers by professional status Count As %
Researcher 2 40%
Student > Master 1 20%
Student > Doctoral Student 1 20%
Other 1 20%
Readers by discipline Count As %
Medicine and Dentistry 2 40%
Biochemistry, Genetics and Molecular Biology 1 20%
Agricultural and Biological Sciences 1 20%
Unspecified 1 20%

Attention Score in Context

This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 03 January 2018.
All research outputs
#10,967,642
of 12,376,381 outputs
Outputs from Journal of Viral Hepatitis
#922
of 1,016 outputs
Outputs of similar age
#292,182
of 351,164 outputs
Outputs of similar age from Journal of Viral Hepatitis
#24
of 29 outputs
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