The polymorphisms in the thyroid peroxidase gene were associated with the development of autoimmune thyroid disease and the serum levels of anti-thyroid peroxidase antibody.

Graves' disease (GD) and Hashimoto's disease (HD) are well known autoimmune thyroid diseases (AITDs), and the severity and intractability of AITDs varies among patients. Thyroid peroxidase (TPO) is a thyroid-specific antigen. The levels of anti-thyroid peroxidase antibody (TPOAb) were higher in patients with HD and may be associated with thyroid destruction. In this study, we genotyped eight single nucleotide polymorphisms (SNPs) in the TPO gene to clarify the association of TPO gene polymorphisms with the development, severity and intractability of AITD. We genotyped TPO rs2071399G/A, rs2071400C/T, rs2071402A/G, rs2071403A/G, rs1126799C/T, rs1126797T/C, rs732609A/C, and rs2048722A/G polymorphisms in 145 patients with GD, 147 patients with HD and 92 healthy controls by PCR-RFLP method. TPO rs2071400 T carriers (CT + TT genotypes) were more frequent in AITD, GD, and HD patients (p=0.0079, 0.0041, and 0.0488, respectively). The TPO rs2071403 GG genotype was more frequent in AITD, GD, and HD patients (p=0.0227, 0.0465, and 0.0305, respectively). There was no significant association between the SNPs and the prognosis of AITD. Serum levels of TPOAb were significantly higher in AITD patients with TPO rs2071400 T carriers (CT + TT genotypes) than in those with the CC genotype (p=0.0295), and were also significantly higher in AITD patients with TPO rs2048722 T carriers (CT + TT genotypes) than in those with the CC genotype (p=0.0056). In conclusion, TPO rs2071400 and rs2071403 polymorphisms were associated with the development of HD and GD, but not with the prognosis. Moreover, TPO rs2071400 and rs2048722 polymorphisms were associated with the serum levels of TPOAb.

Association of the polymorphisms in the gene encoding thyroglobulin with the development and prognosis of autoimmune thyroid disease.

Graves' disease (GD) and Hashimoto's disease (HD) are autoimmune thyroid diseases (AITDs), and the prognosis of AITDs is different for each patient. We examined the association of polymorphisms in the Thyroglobulin (TG) gene with the pathogenesis of AITD. We genotyped TG rs180195G/A, rs853326G/A, rs2076740C/T, rs2703013G/T, rs2958692C/T and rs733735A/G polymorphisms in 137 HD patients, 131 GD patients and 89 healthy controls and also examined the levels of TG mRNA expression and serum TG. The TG rs180195 GG genotype was more frequent in HD patients (p = .0277), and the proportion of CD4+ cells with high levels of TG mRNA was greater in individuals with the GG genotype than in A carriers (p = .0107). The TG rs2703013 TT genotype was less frequent in AITD (p = .0186), and serum TG levels were lower in individuals with the TT genotype than in G carriers (p = .0170). In the TG rs2958692 polymorphism, the T allele was more frequent in intractable GD than in GD in remission (p = .0055), and serum titres of anti-thyroglobulin antibody (TgAb) were lower in GD patients with the TT genotype than in C carriers (p = .0151). In the TG rs2076740 polymorphism, serum titres of TgAb were higher in HD patients who were T carriers than in those with the CC genotype (p = .0359). SNPs in the TG gene were associated with the development of HD and GD, the intractability of GD, and the levels of TG mRNA expression, serum TG, and serum TgAb.