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Updated: Jun 25, 2026
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A High Resolution Method to Monitor Phosphorylation-dependent Activation of IRF3
Published on: January 24, 2016
A polymorphism in MAPKAPK3 affects response to interferon therapy for chronic hepatitis C
Hironobu Tsukada1, Hidenori Ochi, Toshiro Maekawa
1Laboratory for Digestive Diseases, Center for Genomic Medicine, RIKEN (The Institute of Physical and Chemical Research), Kasumi, Minami-ku, Hiroshima, Japan.
Gastroenterology
|February 12, 2009
Summary
Single nucleotide polymorphisms (SNPs) in the MAPKAPK3 gene are linked to interferon therapy outcomes in chronic hepatitis C patients. This finding may improve treatment strategies for hepatitis C virus (HCV) genotype 1b.
Area of Science:
- Genetics
- Hepatology
- Immunology
Background:
- Chronic hepatitis C (HCV) treatment efficacy varies among patients.
- Interferon (IFN) therapy is a standard treatment for HCV.
- Host genetic factors influencing IFN therapy response are not fully understood.
Purpose of the Study:
- To identify host single nucleotide polymorphisms (SNPs) associated with IFN therapy efficacy in chronic hepatitis C patients.
- To investigate the role of type I IFN signaling pathway genes in treatment outcomes.
Main Methods:
- Case-control study of 468 sustained responders and 587 nonresponders to IFN therapy.
- Genotyping of 116 tagging-SNPs in 13 genes involved in type I IFN signaling.
- Functional analysis including allele-specific expression and luciferase reporter assays.
Main Results:
- Two SNPs (rs3792323 and rs616589) in the MAPKAPK3 gene were significantly associated with IFN therapy outcome in HCV genotype 1b patients (P < 5 x 10(-5)).
- rs3792323 was identified as an independent predictor of IFN efficacy.
- Higher allele-specific expression of MAPKAPK3 messenger RNA correlated with nonresponse.
- MAPKAPK3 overexpression inhibited IFN-alfa-induced gene transcription.
Conclusions:
- The SNP rs3792323 in MAPKAPK3 is associated with IFN therapy outcomes in HCV genotype 1b.
- MAPKAPK3 plays a role in inhibiting IFN-alfa-induced antiviral activity, potentially impacting treatment response.
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