Inoue Naoya, Watanabe Mikio, Nakaguchi Azusa, Ueda Daishi, Kawaguti Hayaka, Hidaka Yoh, Iwatani Yoshinori
Department of Biomedical Informatics, Division of Health Sciences, Osaka University Graduate School of Medicine, Suita 565-0871, Japan.
Laboratory for Clinical Investigation, Osaka University Hospital, Suita 565-0871, Japan.
Endocr J. 2017 Jul 28;64(7):695-703. doi: 10.1507/endocrj.EJ16-0551. Epub 2017 May 16.
The prognosis for autoimmune thyroid diseases (AITDs), such as Hashimoto's disease (HD) and Graves' disease (GD), varies among patients. Interleukin (IL)-12 and IL-18 also induce Th1 differentiation, and SOCS1 (Suppressor of cytokine signaling 1) and TIM-3 (T cell immunoglobulin and mucin domain-3) are known to be negative regulators of Th1 cells. To clarify the association of functional polymorphisms in the IL12, IL12Rβ1, IL18, SOCS1 and TIM3 genes with the intractability and severity of autoimmune thyroid disease (AITD), we genotyped these polymorphisms in 151 GD patients, including 61 patients with intractable GD and 51 patients with GD in remission, in 140 HD patients, including 59 patients with severe HD and 55 patients with mild HD, and in 74 healthy controls. The frequency of the IL18 -607CC genotype which correlates with a high production of IL-18, was significantly higher in patients with GD in remission than in those with intractable GD (p=0.0178). The -607C allele was significantly higher in patients with severe HD than in those with mild HD (p=0.0050). The -607CC genotype in IL18 gene may be protective against the intractability of GD, and the -607C allele may enhance the severity of HD.
自身免疫性甲状腺疾病（AITD），如桥本氏病（HD）和格雷夫斯病（GD），患者的预后各不相同。白细胞介素（IL）-12和IL-18也诱导Th1分化，并且已知细胞因子信号传导抑制因子1（SOCS1）和T细胞免疫球蛋白和粘蛋白结构域3（TIM-3）是Th1细胞的负调节因子。为了阐明IL12、IL12Rβ1、IL18、SOCS1和TIM3基因中的功能多态性与自身免疫性甲状腺疾病（AITD）的难治性和严重程度之间的关联，我们对151例GD患者（包括61例难治性GD患者和51例缓解期GD患者）、140例HD患者（包括59例重度HD患者和55例轻度HD患者）以及74名健康对照者进行了这些多态性的基因分型。与IL-18高产生相关的IL18 -607CC基因型的频率在缓解期GD患者中显著高于难治性GD患者（p = 0.0178）。-607C等位基因在重度HD患者中显著高于轻度HD患者（p = 0.0050）。IL18基因中的-607CC基因型可能对GD的难治性具有保护作用，而-607C等位基因可能会加重HD的严重程度。
