HLA-A and DPB1 loci confer susceptibility to Graves' disease

Hum Immunol. 1992 Nov;35(3):165-72. doi: 10.1016/0198-8859(92)90101-r.


To investigate HLA-linked genetic factors involved in the pathogenesis of Graves' disease, 76 patients and 317 healthy controls in the Japanese population were examined for HLA-A, B, C, DR, and DQ specificities by serologic typing and for HLA-DPB1 alleles by DNA typing by using the PCR-SSOP method. The frequencies of HLA-A2, B46, Cw11, and DPB1*0501 were increased and those of HLA-A24, B7, Bw52, and DR1 were decreased in the patients. The increased frequencies of HLA-A2 and DPB1*0501 in the patients were statistically significant when the corrected p value (pc) was applied (pc < 0.02 and pc < 0.002, respectively). ORs for a risk to develop the disease were calculated among individuals positive for DPB1*0501 and/or HLA-A2, and the highest OR (10.5) was observed in individuals possessed both DPB1*0501 and HLA-A2. This observation suggests a synergic involvement of a HLA class II allele (DPB1*0501) and an HLA class I allele (HLA-A2) in the pathogenesis of Graves' disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Amino Acid Sequence
  • Child
  • Disease Susceptibility
  • Female
  • Gene Frequency
  • Genes, MHC Class I / physiology
  • Genes, MHC Class II / physiology
  • Genetic Linkage
  • Graves Disease / genetics*
  • HLA Antigens / genetics
  • HLA-A Antigens / genetics*
  • HLA-DP Antigens / genetics*
  • HLA-DP beta-Chains
  • Humans
  • Immunophenotyping
  • Male
  • Middle Aged
  • Molecular Sequence Data
  • Odds Ratio
  • Polymerase Chain Reaction
  • Polymorphism, Restriction Fragment Length
  • Sequence Homology, Amino Acid


  • HLA Antigens
  • HLA-A Antigens
  • HLA-DP Antigens
  • HLA-DP beta-Chains
  • HLA-DPB1 antigen