Genetic factors in Graves' ophthalmopathy

Clin Endocrinol (Oxf). 1986 Nov;25(5):479-85. doi: 10.1111/j.1365-2265.1986.tb03599.x.


We investigated the distribution of HLA and immunoglobulin G heavy chain markers (Gm) in 117 patients with Graves' disease, 62 with ophthalmopathy and 55 without. With Graves' disease per se, there is a closer association with HLA-DR3 than with B8. The opposite was true for Graves' patients with ophthalmopathy (odds ratio for ophthalmopathy associated with B8 was 12.4 and with DR3 was 7.7, both with P less than 0.0005). HLA-DR7 interacts with B8 in modifying the risk for eye disease; using the phenotype B8- DR7- as reference, the odds ratios were 16.7 for B8+ DR7+, 8.7 for B8+ DR7- and 0.26 for B8- DR7+. Thus, DR7 enhanced the risk for ophthalmopathy in the presence of B8+ but had a protective influence in its absence. Although Gm showed no association with eye disease, it modified the risk for ophthalmopathy associated with HLA-B8; the odds ratios were 20.9 for B8+ Gmfb homozygozity (fb+), 15.3 for B8+ fb- and 1.7 for B8- fb+ (B8- fb- = 1.00). We conclude that the genetic factors contributing to Graves' ophthalmopathy are different from those related to liability for Graves' hyperthyroidism.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Autoimmune Diseases / complications
  • Autoimmune Diseases / genetics*
  • Eye Diseases / etiology
  • Eye Diseases / genetics*
  • Genetic Markers
  • Graves Disease / complications
  • Graves Disease / genetics*
  • HLA Antigens / analysis*
  • HLA-B8 Antigen
  • HLA-DR Antigens / analysis
  • Humans
  • Immunoglobulin Heavy Chains / analysis*


  • Genetic Markers
  • HLA Antigens
  • HLA-B8 Antigen
  • HLA-DR Antigens
  • Immunoglobulin Heavy Chains