a Department of Biomedical Informatics, Division of Health Sciences , Osaka University Graduate School of Medicine , Osaka , Japan.
b Laboratory for Clinical Investigation , Osaka University Hospital , Osaka , Japan.
Autoimmunity. 2017 Sep;50(6):386-392. doi: 10.1080/08916934.2017.1344971. Epub 2017 Jul 4.
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.
格雷夫斯病（GD）和桥本甲状腺炎（HD）是自身免疫性甲状腺疾病（AITD），AITD 患者的预后因人而异。我们研究了甲状腺球蛋白（TG）基因多态性与 AITD 发病机制的关系。我们对 137 例 HD 患者、131 例 GD 患者和 89 名健康对照者的 TG rs180195G/A、rs853326G/A、rs2076740C/T、rs2703013G/T、rs2958692C/T 和 rs733735A/G 多态性进行了基因分型，并检测了 TG mRNA 表达和血清 TG 水平。HD 患者中 TG rs180195 GG 基因型更为常见（p=0.0277），且 GG 基因型个体中高水平 TG mRNA 的 CD4 细胞比例高于 A 携带者（p=0.0107）。TG rs2703013 TT 基因型在 AITD 中较少见（p=0.0186），TT 基因型个体的血清 TG 水平低于 G 携带者（p=0.0170）。在 TG rs2958692 多态性中，难治性 GD 患者的 T 等位基因比缓解期 GD 患者更为常见（p=0.0055），TT 基因型 GD 患者的抗甲状腺球蛋白抗体（TgAb）血清滴度低于 C 携带者（p=0.0151）。在 TG rs2076740 多态性中，TG 携带者的 HD 患者的 TgAb 血清滴度高于 CC 基因型患者（p=0.0359）。TG 基因的 SNP 与 HD 和 GD 的发病、GD 的难治性以及 TG mRNA 表达、血清 TG 和血清 TgAb 水平有关。
