GENETIC FACTORS IN GRAVES' OPHTHALMOPATHY

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Abstract
We investigated the distribution of HLA and immunoglobulin G heavy chain markers (Gm) in 117 patients with Graves'' disease, 62 with ophthalmopthy 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 < 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 homozygosity (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.

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