ASSOCIATION OF GRAVES-DISEASE WITH AN ALLELE OF THE INTERLEUKIN-1 RECEPTOR ANTAGONIST GENE

The proinflammatory cytokine, interleukin-1 (IL-1), has been implicate d in the pathogenesis of several autoimmune and inflammatory diseases. One of its natural inhibitors, IL-1 receptor antagonist, is a potent antiinflammatory agent. We have previously described genetic associati ons between an allele of the IL-1 receptor antagonist gene (IL1RN2) a nd several autoimmune and inflammatory diseases. In the present study, we tested the association of this polymorphism with thyroid diseases. We genotyped 2 separate cohorts (total of 100 patients) with Graves' disease and 58 patients with Hashimoto's thyroiditis and compared IL1R N2 frequencies with those in 261 ethnically matched controls. There w as a significant increase in IL1RN2 frequency and carriage rate in Gr aves' disease, but this was not associated with thyroid antibody level s, T-4 levels, thyroid-associated ophthalmopathy, or outcome after ant ithyroid drug treatment. In contrast, there was no difference in the f requency of IL1RN2 between patients with Hashimoto's thyroiditis and the control group. Whether the IL1RN polymorphism makes a direct funct ional contribution to the pathogenesis of Graves' disease or is acting as a marker for a linked gene is being investigated.