A Polymorphism of Interferon-γ Gene Associated with Changes of Anti-Thyrotropin Receptor Antibodies Induced by Antithyroid Drug Treatment for Graves' Disease in Japanese Patients

Graves' disease (GD) is an autoimmune disorder with genetic predisposition. Interferon-γ (IFN-γ) is an important mediator of inflammatory and immune responses. The aim of the present study was to investigate whether the polymorphism of IFN-γ gene is associated with the development of GD or with clinical course during the antithyroid drug therapy. We have studied the CA repeat polymorphisms in the first intron of IFN γ gene in Japanese patients with GD (n = 162) and healthy control subjects without antithyroid autoantibodies or family history of autoimmune disorders (n= 133). There was no difference in allele frequency of IFN-γ gene polymorphism between patients with GD and control subjects. However, the allele 4 (15 CA repeats) frequency was significantly greater in patients whose antithyrotropin receptor antibody (TRAb) became negative within 3 years by antithyroid drug treatment than those with consistently positive TRAb for more than 3 years (34.1% vs. 15.7%,χ² = 8.545, p = 0.0035, pc = 0.049). The in vitro production of IFN-γ by concanavalin A-stimulated peripheral blood mononuclear cells was significantly smaller in control subjects with the allele 4 compared to those with the other alleles. In conclusions, the CA repeat polymorphism of the IFN-γ gene might be associated with the outcome of anti-thyroid drug treatment.