HLA-DRB3 gene alleles in Caucasian patients with Graves' disease

Clin Investig. 1992 Oct;70(10):956-60. doi: 10.1007/BF00180447.


Graves' disease (GD) is a human leukocyte antigen (HLA) linked organ-specific autoimmune disease. In German GD patients the disease is associated with HLA specificities of the HLA-DRw52 family (HLA-DR3, -DR5, and DR6; HLA-DRB3 positive HLA haplotypes). Recently, a strong association with a HLA-DRB3 restriction fragment length polymorphism gene has been described. To study HLA-DRB3 alleles and their association with the disease, a large cohort of controls (n = 3724) and GD patients (n = 304) was analyzed. HLA-DR allelic combinations revealed an increase in HLA-DR3/DR5 heterozygous patients (relative risk 2.9; P < 0.001). HLA-DRB3 alleles, as defined by DNA typing in HLA-DR matched groups revealed a significant increase in DRB3*0101 homozygosity (relative risk 17.5; P < 0.001) in HLA-DR3 homozygous patients. In GD patients with ophthalmopathy (grade II or higher, according to Werner) DRB3*0101/*0202 heterozygosity revealed an increased relative risk of 5.5 (P < 0.001). Non-HLA-DR3 homozygous, DRB3*0101/*0202 heterozygous patients were at the highest risk for endocrine ophthalmopathy (relative risk 10; P < 0.001). Our data, based on DNA typing methods of HLA-D genes, provide evidence that the susceptibility is strongly associated with HLA-DRB3 genes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • Base Sequence
  • Biomarkers / blood
  • DNA / analysis
  • Graves Disease / genetics*
  • HLA-DR Antigens / genetics*
  • HLA-DRB3 Chains
  • Heterozygote
  • Humans
  • Molecular Sequence Data
  • Polymerase Chain Reaction
  • Retrospective Studies
  • Risk Factors
  • Serologic Tests
  • Whites / genetics*


  • Biomarkers
  • HLA-DR Antigens
  • HLA-DRB3 Chains
  • DNA