a Department of Biomedical Informatics, Division of Health Sciences , Osaka University Graduate School of Medicine , Suita , Osaka , Japan.
b Laboratory for Clinical Investigation , Osaka University Hospital , Suita , Osaka , Japan.
Autoimmunity. 2018 Feb;51(1):35-42. doi: 10.1080/08916934.2017.1416468. Epub 2017 Dec 19.
The microRNA (miRNA) biogenesis pathway is regulated by specific proteins and enzymes, including Dicer, Drosha, DGCR8, Exportin 5 and the Argonaute (AGO) family. In this study, we investigated the AGO family, which is the primary component of RISC (RNA-induced silencing complex) and directly binds to microRNA. We examined the association of polymorphisms in AGO family genes with AGO expression and with the development and prognosis of autoimmune thyroid diseases. We genotyped AGO1 rs636832A/G, AGO2 rs7005286C/T, AGO2 rs11166985A/G and AGO2 rs2292779C/G polymorphisms in 184 Graves' disease (GD) patients, 195 Hashimoto's disease (HD) patients and 122 healthy volunteers using the polymerase chain reaction-restriction fragment length polymorphism method. We also examined the expression of AGO1 and AGO2 mRNAs in peripheral blood mononuclear cells (PBMC) obtained from 52 GD patients, 41 HD patients, and 25 healthy volunteers using quantitative RT-PCR methods. The G allele of AGO1 rs636832 and the A allele of AGO2 rs11166985 polymorphisms were significantly more frequent in GD patients than in healthy controls. The A allele of AGO2 rs11166985 was also significantly more frequent in intractable GD patients than in controls. The C carrier (CC + CG genotypes) and C allele of AGO2 rs2292779 polymorphism were significantly more frequent in intractable GD patients than in patients with GD in remission. Expression of AGO1 mRNA in PBMC was significantly higher in AITD patient than in controls, and that of AGO2 mRNA in PBMC was significantly higher in intractable GD patients than in patients with GD in remission. Furthermore, the expression levels of both the AGO1 and AGO2 genes were significantly correlated with the proportions of Th17 cells in PBMC. In conclusion, the polymorphisms of the AGO1 and AGO2 genes, the expression levels of which correlated with the proportion of Th17 cells, were associated with the development and prognosis of GD. The AGO2 rs2292779 C carrier and C allele were associated with the intractability of GD.
微小 RNA (miRNA) 的生物发生途径受到特定蛋白质和酶的调节，包括 Dicer、Drosha、DGCR8、Exportin 5 和 Argonaute (AGO) 家族。在这项研究中，我们研究了 AGO 家族，AGO 家族是 RISC（RNA 诱导沉默复合物）的主要组成部分，直接与 microRNA 结合。我们研究了 AGO 家族基因多态性与 AGO 表达以及自身免疫性甲状腺疾病的发生和预后的关系。我们使用聚合酶链反应-限制性片段长度多态性方法，对 184 例格雷夫斯病（GD）患者、195 例桥本甲状腺炎（HD）患者和 122 例健康志愿者进行了 AGO1 rs636832A/G、AGO2 rs7005286C/T、AGO2 rs11166985A/G 和 AGO2 rs2292779C/G 多态性的基因分型。我们还使用定量 RT-PCR 方法检测了 52 例 GD 患者、41 例 HD 患者和 25 例健康志愿者外周血单个核细胞（PBMC）中 AGO1 和 AGO2 mRNA 的表达。AGO1 rs636832 的 G 等位基因和 AGO2 rs11166985 的 A 等位基因在 GD 患者中明显比健康对照组更常见。AGO2 rs11166985 的 A 等位基因在难治性 GD 患者中也明显比对照组更常见。AGO2 rs2292779 的 C 携带者（CC+CG 基因型）和 C 等位基因在难治性 GD 患者中明显比缓解期 GD 患者更常见。AITD 患者 PBMC 中的 AGO1 mRNA 表达明显高于对照组，而难治性 GD 患者 PBMC 中的 AGO2 mRNA 表达明显高于缓解期 GD 患者。此外，AGO1 和 AGO2 基因的表达水平与 PBMC 中 Th17 细胞的比例显著相关。总之，与 Th17 细胞比例相关的 AGO1 和 AGO2 基因的多态性与 GD 的发生和预后相关。AGO2 rs2292779 的 C 携带者和 C 等位基因与 GD 的难治性相关。
