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

Dig Liver Dis. 2022 Feb;54(2):228-236. doi: 10.1016/j.dld.2021.04.010. Epub 2021 May 17.


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. DRB1×07:01, 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 β54, β59 and β66 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.

Keywords: Amino acid residues; HLA-DRB1 alleles; Pedigree; Primary biliary cholangitis.

MeSH terms

  • Aged
  • Alleles
  • Exome Sequencing
  • Female
  • Genetic Predisposition to Disease / genetics*
  • Genotype
  • HLA-DRB1 Chains / genetics*
  • Humans
  • Liver Cirrhosis, Biliary / genetics*
  • Male
  • Middle Aged
  • Mutation, Missense
  • Polymorphism, Genetic
  • Risk Factors


  • HLA-DRB1 Chains