IL28B genotype and the expression of ISGs in normal liver

Authors

  • Zoe Raglow,

    1. Department of Pharmacology, Toxicology & Therapeutics, University of Kansas Medical Center, Kansas City, KS, USA
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  • Carly Thoma-Perry,

    1. Department of Pharmacology, Toxicology & Therapeutics, University of Kansas Medical Center, Kansas City, KS, USA
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  • Richard Gilroy,

    1. Department of Medicine, University of Kansas Medical Center, Kansas City, KS, USA
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  • Yu-Jui Y. Wan

    Corresponding author
    1. Department of Medical Pathology and Laboratory Medicine, University of California Davis, Sacramento, CA, USA
    • Department of Pharmacology, Toxicology & Therapeutics, University of Kansas Medical Center, Kansas City, KS, USA
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Correspondence

Yu-Jui Y. Wan, Department of Medical Pathology and Laboratory Medicine, University of California, Davis 4645 Second Avenue Sacramento, CA 95817, USA

Tel: +916 734 4293

Fax: +916 734 3787

e-mail: yjywan@ucdavis.edu

Abstract

Background & Aims

Both polymorphisms in the IL28B gene locus and ISG expression levels are associated with the outcome of hepatitis C virus (HCV) infection. The two are also interrelated, although the mechanism is unknown. Favourable CC genotype at rs12979860 expresses lower baseline ISG levels and responds better to treatment than unfavourable CT and TT genotypes. Little is known about this relationship in normal, uninfected liver. This study sought to explore this relationship.

Methods

Normal human liver specimens (64) and HCV positive human liver specimens (95) were genotyped for IL28B rs12979860 C > T. mRNA levels of ISGs and other relevant genes were studied by qPCR.

Results

Most studied ISGs had significantly different expression by IL28B genotype in normal liver. CC genotype expressed the highest levels, CT intermediate and TT the lowest. This is opposite to the pattern seen in HCV patients. Principal component analysis of IL28B genotype and ISG expression further revealed a distinct set of genes correlated with the C allele (ISG15, HTATIP2, LGALS3BP, IRF2 and BCL2) and T allele (IFNα, β, γ, λ3 and CD80).

Conclusion

A subset of ISGs was found to be differentially expressed in normal liver by IL28B genotype. This suggests a relationship between IL28B genotype and gene expression before HCV infection.

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