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A regulatory polymorphism in interferon-γ receptor 1 promoter is associated with the susceptibility to chronic hepatitis B virus infection

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Abstract

The antiviral cascade triggered by interferon-γ (IFN-γ) represents a vital event for eradicating hepatitis B virus (HBV) in experimental animals. IFN-γ signaling is mediated through the ligand binding to IFN-γ receptor 1 (IFNGR1). Control of IFNGR1 expression level is one of the mechanisms by which cells modulate the potency of IFN-γ signaling. In this study, we comprehensively investigated the single nucleotide polymorphisms (SNPs) in IFNGR1 gene and correlated their occurrence to susceptibility to HBV infection in a Chinese population. A total of 983 participants, including 361 chronic hepatitis B patients, 256 individuals who had spontaneously recovered from HBV infection, and 366 healthy control subjects, were enrolled in the study. Polymerase chain reaction-restriction fragment length polymorphism was used to identify seven SNPs (–611A/G, –56C/T, 40G/A, 95C/T, 130A/G, 20685A/G, 21227T/C) in IFNGR1 gene. We found that –56C and –56T allele were associated with viral clearance and viral persistence, respectively (P = 0.014). In a reporter-driven assay, we validated that the promoter variant with –56C exhibited a higher transcription level than that with –56T in HepG2 cells in a cell-type-specific pattern. We conclude that a functional –56C/T SNP in IFNGR1 promoter is associated with the clinical outcome of HBV infection in this Chinese population.

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Abbreviations

IFN-γ:

Interferon-γ

IFNGR1:

IFN-γ receptor 1

HBV:

Hepatitis B virus

SNP:

Single nucleotide polymorphism

CHP:

Chronic hepatitis B patients

SRI:

Spontaneous recovered individuals

HCS:

Healthy control subjects

PCR-RFLP:

Polymerase chain reaction-restriction fragment length polymorphism

LD:

Linkage disequilibrium

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Acknowledgement

This work was supported in part by the University Development Fund of the University of Hong Kong.

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Author notes

  1. Jie Zhou

    Present address: Northern California Institute for Research and Education, San Francisco, CA, USA

Authors and Affiliations

  1. Department of Microbiology, The University of Hong Kong, Pokfulam, Hong Kong, Hong Kong SAR, China

    Jie Zhou, Ding-Qiang Chen, Vincent K. M. Poon, Yong Zeng, Fai Ng, Kwok-Yung Yuen & Bo-Jian Zheng

  2. Research Centre of Infection and Immunology, The University of Hong Kong, Hong Kong, Hong Kong SAR, China

    Liwei Lu, Kwok-Yung Yuen & Bo-Jian Zheng

  3. Department of Pathology, The University of Hong Kong, Hong Kong, Hong Kong SAR, China

    Liwei Lu

  4. Department of Biochemistry, The University of Hong Kong, Hong Kong, Hong Kong SAR, China

    Jian-Dong Huang

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  1. Jie Zhou
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Corresponding author

Correspondence to Bo-Jian Zheng.

Additional information

J. Zhou and D.-Q. Chen contributed to this study equally.

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Zhou, J., Chen, DQ., Poon, V.K.M. et al. A regulatory polymorphism in interferon-γ receptor 1 promoter is associated with the susceptibility to chronic hepatitis B virus infection. Immunogenetics 61, 423–430 (2009). https://doi.org/10.1007/s00251-009-0377-8

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  • DOI: https://doi.org/10.1007/s00251-009-0377-8

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