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Variation and expression of HLA-DPB1 gene in HBV infection

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Abstract

Hepatitis B virus (HBV) affects approximately 68 million people in China, and 10–15% of adults infected with HBV develop chronic hepatitis B, liver cirrhosis, liver failure or hepatocellular carcinoma (HCC). HLA-DPB1 gene polymorphism and expression have been shown to be associated with HBV infection susceptibility and spontaneous clearance. The aim of this study is to evaluate the role of HLA-DPB1 gene polymorphism in HBV infection. HLA-DPB1 and rs9277535 polymorphisms were investigated in 259 patients with HBV infection and 442 healthy controls (HCs) using sequence-based typing. The mRNA of HLA-DPB1 was measured by real-time polymerase chain reaction. HLA-DPB1 genes and rs9277535 polymorphisms were all associated with HBV infection in the Sichuan Han population. rs9277535A and HLA-DPB1*04:02 played a protective role against HBV infection. rs9277535G and DPB1*05:01 were associated with susceptibility to HBV infection. rs9277535GG had significantly higher HLA-DPB1 mRNA expression in the HBV infection group compared with the HC group. HLA-DPB1*05:01 and HLA-DPB1*21:01 had significantly lower mRNA expression in the HBV infection group compared with the HC group. The meta-analysis revealed that HLA-DPB1*02:01, HLA-DPB1*02:02, HAL-DPB1*04:01 and HLA-DPB1*04:02 protected against HBV infection, while HLA-DPB1*05:01, HLA-DPB1*09:01, and HLA-DPB1*13:01 were risk factors for susceptibility to HBV infection. HLA-DPB1*02:01, HLA-DPB1*02:02, and HLA-DPB1*04:01 were associated with HBV spontaneous clearance, while HLA-DPB1*05:01 was associated with chronic HBV infection. HLA-DPB1 alleles and rs9277535 have a major effect on the risk of HBV infection, and HBV infection is associated with lower HLA-DPB1 expression. HLA-DPB1 alleles have an important role in HBV susceptibility and spontaneous clearance.

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Data availability

All the data and materials supporting the conclusions were included in the main paper.

Abbreviations

HBV:

Hepatitis B virus

HLA:

Human leukocyte antigens

APCs:

Antigen-presenting cells

CHB:

Chronic HBV carriers

HC:

Healthy controls

HBsAg:

Hepatitis B surface antigen

HBsAb:

Hepatitis B surface antibody

HBeAg:

Hepatitis Be antigen

HBeAb:

Hepatitis Be antibody

HBcAb:

Hepatitis core antibody

HCV:

Hepatitis C virus

HIV:

Human immunodeficiency virus

HWE:

Hardy–Weinberg equilibrium

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Acknowledgments

The authors thank the participants for generously providing the venous blood samples.

Funding

This work was supported by the CAMS Innovation Fund for Medical Sciences (CIFMS) under contract 2016-I2M-3–024, Funding of Sichuan Science and Technology Department under contract 2017RZ0047 and 2018SZ0395 and Ministry of Science and Technology of China, Grant/Award number: 2014EG150133. The CIFMS program provided us blood samples and relevant data, funding of Sichuan Science and Technology Department project provide us the cytokine detect methods and methods of HLA-DPB1 typing, program of Ministry of Science and Technology of China provide us HBV relevant detect methods.

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Authors and Affiliations

  1. Department of Laboratory Medicine, West China Second University Hospital, Chengdu, Sichuan, China

    Guojin Ou & Xiaojuan Liu

  2. Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, Chengdu, Sichuan, China

    Guojin Ou & Xiaojuan Liu

  3. Deyang People’s Hospital, Deyang, Sichuan, China

    Xiao Liu

  4. Clinical Blood Transfusion Research Center, Institute of Blood Transfusion, CAMS & PUMC, Chengdu, Sichuan, China

    Haixia Xu, Xin Ji & Jue Wang

  5. Key Laboratory of Transfusion Adverse Reactions, CAMS & PUMC, Chengdu, Sichuan, China

    Haixia Xu, Xin Ji & Jue Wang

Authors
  1. Guojin Ou
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  2. Xiao Liu
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  3. Haixia Xu
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  4. Xin Ji
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  5. Xiaojuan Liu
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  6. Jue Wang
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Contributions

Ou GJ, Xu HX, and Ji X performed the experiments. Liu X collected and evaluated the samples. Ou GJ and Liu XJ wrote the original draft of the manuscript. Wang J and Liu XJ designed the experiments and performed the data analysis, discussed the results, and substantially revised the manuscript.

Corresponding authors

Correspondence to Xiaojuan Liu or Jue Wang.

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Ethics approval and consent to participate

This study was approved by the ethic committees of the Institution of Blood Transfusion, CAMS&PUMC, and was conducted according to the principles of the Declaration of Helsinki. All participants provided written informed consent before enrolment, and the study’s protocol was approved by the ethic committees of the Institution of Blood Transfusion, CAMS&PUMC.

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The authors declare that they have no competing interests.

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Ou, G., Liu, X., Xu, H. et al. Variation and expression of HLA-DPB1 gene in HBV infection. Immunogenetics 73, 253–261 (2021). https://doi.org/10.1007/s00251-021-01213-w

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  • DOI: https://doi.org/10.1007/s00251-021-01213-w

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