Functional Polymorphisms of the Type 1 and Type 2 Iodothyronine Deiodinase Genes in Autoimmune Thyroid Diseases
Functional Polymorphisms of the Type 1 and Type 2 Iodothyronine Deiodinase Genes in Autoimmune Thyroid Diseases
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DOI：
10.1080/08820139.2018.1458861
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发表时间：
2018-01-01
影响因子：
2.8
通讯作者：
Iwatani, Yoshinori
中科院分区：
文献类型：
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作者：
Inoue, Naoya;Watanabe, Mikio;Iwatani, Yoshinori
Graves病(GD)和桥本病(HD)是主要的自身免疫性甲状腺疾病(AITD)，其病理状态因患者而异。甲状旁腺原氨酸脱碘酶(D1)和甲状旁腺原氨酸脱碘酶(D2)由甲状腺激素(T4)转化为三碘甲腺原氨酸(T3)。然而，关于D1和D2基因的多态与AITD之间的关联的研究还很少。因此，我们采用聚合酶链式反应-限制性片段长度多态性方法对134例GD患者进行了D1rs11206244、D2rs225014和rs12885300的基因分型，其中难治性GD 54例，缓解期44例，HD 132例，其中重度HD 57例，轻度HD 45例，正常对照84例。在D2rs225014基因多态中，AITD患者，尤其是HD患者中，与D2活性相关的TT基因频率明显低于对照组(P分别为0.0032和0.0002)。HD组较GD组发生率低(P=0.0199)。重度HD组和轻度HD组TT基因型和T等位基因频率均低于对照组(P分别为0.0003、0.0006、0.0432和0.0427)。TT型D2rs225014多态频率低与AITD的发生和HD的严重程度相关。
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.