Human leucocyte antigen alleles and haplotypes and their associations with antinuclear antibodies features in Chinese patients with primary biliary cirrhosis

Authors

  • Dan-Tong Zhao,

    1. Clinical Research Center for Autoimmune Liver Disease, Beijing You'an Hospital, Capital Medical University, Beijing, China
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    • Both authors share first authorship.
  • Hui-Yu Liao,

    1. Clinical Research Center for Autoimmune Liver Disease, Beijing You'an Hospital, Capital Medical University, Beijing, China
    2. Department of Liver Disease Immunology, Beijing You'an Hospital, Capital Medical University, Beijing, China
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    • Both authors share first authorship.
  • Xin Zhang,

    1. Clinical Research Center for Autoimmune Liver Disease, Beijing You'an Hospital, Capital Medical University, Beijing, China
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  • Yan-Min Liu,

    1. Clinical Research Center for Autoimmune Liver Disease, Beijing You'an Hospital, Capital Medical University, Beijing, China
    2. Department of Liver Disease Immunology, Beijing You'an Hospital, Capital Medical University, Beijing, China
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  • Yan Zhao,

    1. Clinical Research Center for Autoimmune Liver Disease, Beijing You'an Hospital, Capital Medical University, Beijing, China
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  • Hai-Ping Zhang,

    1. Clinical Research Center for Autoimmune Liver Disease, Beijing You'an Hospital, Capital Medical University, Beijing, China
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  • Li-Mei Sun,

    1. Clinical Research Center for Autoimmune Liver Disease, Beijing You'an Hospital, Capital Medical University, Beijing, China
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  • Yin-Xue Ma,

    1. Clinical Research Center for Autoimmune Liver Disease, Beijing You'an Hospital, Capital Medical University, Beijing, China
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  • Hui-Ping Yan

    Corresponding author
    1. Clinical Research Center for Autoimmune Liver Disease, Beijing You'an Hospital, Capital Medical University, Beijing, China
    • Correspondence

      Professor Hui-Ping Yan, Clinical Research Center for Autoimmune Liver Disease, Beijing You'an Hospital, Capital Medical University, No.8 Xitoutiao, Youanmen Wai, Fengtai District, 100069 Beijing, China.

      Tel: +011 86 10 83997347

      Fax: +011 86 10 63291531

      e-mail: yhp503@126.com

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Abstract

Background & Aims

Primary biliary cirrhosis (PBC) is an autoimmune liver disease. Genetic factors are critical in determining susceptibility to PBC. Among human leuocyte antigen (HLA) genes, an association between the DRB1*08 allele and PBC has been reported in many populations, but not in Chinese patients.

Methods

We investigated HLA-A, B, DRB1, and DQB1 alleles and haplotypes in 145 PBC patients and 500 healthy subjects. Patients were also stratified according to autoantibody features, and associations between these and HLA alleles were analyzed.

Results

Significant associations existed between HLA-DRB1*08:03 (22.1% vs. 9.0%, Pc < 0.0001, OR = 2.86), DQ2 (41.4% vs. 25.4%, Pc < 0.0001, OR = 2.07) and DQB1*06:01 (31.0% vs. 17.8%, Pc = 0.014, OR = 2.08) alleles and PBC. DRB1*08:03-DQB1*06:01 (22.1% vs. 8.2%, < 0.0001, OR = 3.17) and DRB1*07:01-DQB1*02:02 haplotypes (28.3% vs. 17.6%, = 0.005, OR = 1.85) were also associated with PBC susceptibility. In contrast, the DQB1*03:01 allele (21.4% vs. 39.2%, Pc < 0.0001, OR = 0.42) and DRB1*12:02-DQB1*03:01 haplotype (6.9% vs. 14.6%, = 0.015, OR = 0.43) were significantly decreased in PBC patients compared with controls. DRB1*14:54 and DQ5(1) protected against antinuclear antibody (ANA) (OR = 0.25) and anti-gp210 antibody (OR = 0.39) production, respectively, while HLA-B*44:03 predisposed patients to anti-gp210 antibody (OR = 5.70) production.

Conclusion

These results suggest that Chinese patients with PBC have a distinct genetic background in eastern Asia, and we confirmed the role of HLA genes in determining PBC susceptibility and autoantibody features in the Chinese population.

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