Functional Polymorphisms of the Type 1 and Type 2 Iodothyronine Deiodinase Genes in Autoimmune Thyroid Diseases

Graves' disease (GD) and Hashimoto's disease (HD) are major autoimmune thyroid diseases (AITDs), and their pathological conditions vary among patients. Type 1 iodothyronine deiodinase (D1) and type 2 iodothyronine deiodinase (D2) convert from thyroxine (T4) to triiodothyronine (T3). However, few findings have been described concerning the association between polymorphisms in D1 and D2 genes and AITD. Therefore, we genotyped D1 rs11206244, D2 rs225014, and rs12885300 polymorphisms in 134 GD patients, including 54 patients with intractable GD and 44 patients with GD in remission and 132 HD patients, including 57 patients with severe HD, 45 patients with mild HD, and 84 healthy controls using PCR-RFLP. In the D2 rs225014 polymorphism, the TT genotype, which was correlated with higher D2 activity, was less frequent in AITD, especially in HD, than in control subjects (P = 0.0032 and 0.0002, respectively). Moreover, they were also less frequent in HD than in GD (P = 0.0199). The TT genotype and T allele were less frequent in severe HD and mild HD than in control subjects (P = 0.0003, 0.0006, 0.0432, and 0.0427, respectively). In conclusion, the low frequency of the TT genotype D2 rs225014 polymorphism was associated with the development of AITD and severity of HD.