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IL6 gene allele-specific C/EBPα-binding activity affects the development of HBV infection through modulation of Th17/Treg balance

Genes & Immunity volume 16, pages 528–535 (2015)Cite this article

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Abstract

Interleukin-6 (IL-6) has an important role in the pathogenesis of chronic viral hepatitis and related liver diseases. Although host genetics associated with the response to anti-viral treatment have been reported, little is known about the relationship between IL6 genetic polymorphisms and the outcome of hepatitis B virus (HBV) infection. In this study, we determined the genotype distribution of rs1800796 polymorphism in healthy controls and cases including chronic HBV (CHB), hepatitis C virus and HIV infection. The rs1800796 was found to be associated with clinical outcome of CHB in experimental and validation cohort. The rs1800796C allele has twofold higher promoter activity than G allele. Consistently, CD14+ monocytes from subjects carrying the rs1800796C allele produced more IL-6 in response to in vitro HBV core antigen stimulation than those carrying G allele. Moreover, CHB patients carrying rs1800796C allele have significantly higher T-helper 17 (Th17) and regulatory T cell (Treg) ratio. Finally, a transcription factor C/EBPα binds in higher affinity to rs1800796C allele than to G allele. These results suggest that genetic predisposition to higher IL-6 production is associated with increased risk to HBV infection and hepatic inflammation, which might be due to C/EBPα-mediated regulatory effect on Th17 and Treg responses. Appropriate manipulation of IL-6 expression might be used to prevent and treat HBV infection.

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Acknowledgements

This study was supported by Natural Science Foundation of China (numbers 81172732 and 81501714); Guangdong Key Laboratory of Emerging Infectious Diseases; Natural Science Foundation of Guangdong (number 2014A030313789); Shenzhen Key Laboratory of Infection and Immunity; and Shenzhen Scientific and Technological Foundation (number JCYJ20140411111 718166). We thank staffs, doctors and nurses of Shenzhen Third People’s Hospital for patient management, sample collection and analysis in this work.

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  1. G Zhang, W Wang and S Li: These authors contributed equally to this work.

Authors and Affiliations

  1. Guangdong Key Laboratory of Emerging Infectious Diseases, Shenzhen Third People’s Hospital, Guangdong Medical College, Shenzhen, China

    G Zhang, W Wang, S Li, M Zhang, P Zhang, B Zhou & X Chen

  2. Department of Clinical Laboratory, Guangzhou Medical University, Guangzhou, China

    H Yang & A Wu

  3. Department of Chest Surgery, Shenzhen People’s Hospital, Jinan University, Shenzhen, China

    Y Wen & L Yang

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Correspondence to B Zhou or X Chen.

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Zhang, G., Wang, W., Li, S. et al. IL6 gene allele-specific C/EBPα-binding activity affects the development of HBV infection through modulation of Th17/Treg balance. Genes Immun 16, 528–535 (2015). https://doi.org/10.1038/gene.2015.40

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