Association of functional polymorphisms related to the transcriptional level of FOXP3 with prognosis of autoimmune thyroid diseases

Summary The severity of Hashimoto's disease (HD) and intractability (or inducibility to remission) of Graves' disease (GD) varies among patients. Forkhead box P3 (FoxP3) is a crucial regulatory factor for the development and function of regulatory T (Treg) cells, and deficiency of the FoxP3 gene (FOXP3) suppresses the regulatory function of Treg cells. To clarify the association of the functional polymorphisms of the FOXP3 with the prognosis of GD and HD, we genotyped −3499A/G, −3279C/A and −2383C/T polymorphisms in FOXP3 gene obtained from 38 patients with severe HD, 40 patients with mild HD, 65 patients with intractable GD, in whom remission was difficult to induce, 44 patients with GD in remission and 71 healthy volunteers. The −3279CA genotype was more frequent in patients with GD in remission than in patients with intractable GD, and the −3279AA genotype, which correlates to defective transcription of FOXP3, was absent in patients with GD in remission. The −2383CC genotype was more frequent in patients with severe HD than in those with mild HD. In conclusion, the −3279A/C polymorphism is related to the development and intractability of GD and the −2383CC genotype to the severity of HD.