Primary role of the HLA class II DRB1*0301 allele in Graves disease

Am J Med Genet. 2000 Dec 18;95(5):432-7. doi: 10.1002/1096-8628(20001218)95:5<432::aid-ajmg5>;2-7.


The association of the Graves disease (GD) with HLA DR3 and DQA1*0501 in Caucasians has been described previously. From these studies it could not be determined whether one specific locus was primarily involved. Using a case-control study design, we have examined the role of HLA class II gene polymorphisms in the predisposition for GD in a group of Belgian subjects. We demonstrated that both DRB1*0301 and DQA1*0501 alleles conferred significant susceptibility in the DRB1*0301-DQA1*0501 haplotype. The DRB1*0301 allele was the primary susceptibility allele for GD, however, because the susceptibility provided by DQA1*0501 was most likely due to it being in linkage disequilibrium with DRB1*0301. The DRB1*0701/x and DQA1*0201/x genotypes and the DRB1*0701-DQA1*0201 haplotype provided protection with an equal RR of 0.29. Predictive value calculations showed that testing for DRB1*0301 gave the highest positive predictive value for GD in females and males. This was, however, 10 times higher in females and predicted a 3.63% risk for a random female to develop GD.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • DNA / analysis
  • Disease Susceptibility
  • Female
  • Genotype
  • Graves Disease / genetics*
  • Graves Disease / immunology
  • Graves Disease / prevention & control
  • HLA-DR Antigens / classification
  • HLA-DR Antigens / genetics*
  • HLA-DRB1 Chains
  • Haplotypes
  • Humans
  • Male
  • Polymerase Chain Reaction
  • Polymorphism, Genetic
  • Predictive Value of Tests
  • Prognosis
  • Risk Assessment
  • Sensitivity and Specificity


  • HLA-DR Antigens
  • HLA-DRB1 Chains
  • HLA-DRB1*03:01 antigen
  • DNA