Genetic factors in Graves' ophthalmopathy.
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.
D001327:Autoimmune Diseases / Q000150:complications / Q000235:genetics*; D005128:Eye Diseases / Q000209:etiology / Q000235:genetics*; D005819:Genetic Markers; D006111:Graves Disease / Q000150:complications / Q000235:genetics*; D006680:HLA Antigens / Q000032:analysis*; D015795:HLA-B8 Antigen; D006684:HLA-DR Antigens / Q000032:analysis; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000032:analysis*
D005819:Genetic Markers; D006680:HLA Antigens; D015795:HLA-B8 Antigen; D006684:HLA-DR Antigens; D007143:Immunoglobulin Heavy Chains