Novel HLA-DRB1 alleles contribute risk for disease susceptibility in primary biliary cholangitis

Yanni Li, Xin Liu, Yi Wang, Yi Zhou, Shixian Hu, Hui Yang, Weilong Zhong, Jingwen Zhao, Xiaoyi Wang, Hongyu Chu, Yanping Zheng, Jie Zhang, Lu Zhou, Bangmao Wang

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    Background: Primary biliary cholangitis (PBC) is a complex disease with high heritability. We investigated the association between human leukocyte antigen (HLA)-DRB1 alleles and PBC in families and sporadic cases to evaluate the genetic components of the disease. Methods: We performed whole exome sequencing in three PBC families. We genotyped HLA-DRB1 and calculated the association between HLA-DRB1 alleles and the encoding amino acid sequences with the clinical features. Results: Ten variants harboured the HLA-DRB1 gene associated with PBC. DRB1 x07:01, 14:01 and 14:05 were highly increased in PBC. Ten coding region polymorphisms were associated with PBC that encode the amino acid variants of HLA-DR beta 54, beta 59 and beta 66 located in the peptide-binding site of the MHC molecule. Glutamine at position 54 was confirmed as a risk amino acid, verifying the results of familial aggregation analysis of PBC families. Discussion: Familial aggregation analysis indicated that HLA-DRB1 is a candidate gene for the risk of disease course. Considering that amino acid variations are critical to peptide-binding properties, they underlie the major component of MHC association with PBC. (c) 2021 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

    Original languageEnglish
    Pages (from-to)228-236
    Number of pages9
    JournalDigestive and Liver Disease
    Issue number2
    Early online date17-May-2021
    Publication statusPublished - Feb-2022


    • Primary biliary cholangitis
    • HLA-DRB1 alleles
    • Amino acid residues
    • Pedigree
    • GENE

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