Saeki Minori, Watanabe Mikio, Inoue Naoya, Tokiyoshi Ena, Takuse Yukina, Arakawa Yuya, Hidaka Yoh, Iwatani Yoshinori
a Department of Biomedical Informatics, Division of Health Sciences , Osaka University Graduate School of Medicine , Osaka , Japan and.
b Laboratory for Clinical Investigation , Osaka University Hospital , Osaka , Japan.
Autoimmunity. 2016 Dec;49(8):514-522. doi: 10.1080/08916934.2016.1230846. Epub 2016 Nov 3.
Dicer and Drosha are RNase III enzymes that are necessary for the biogenesis of most miRNAs. However, there are no reports on the association of Dicer and Drosha with the pathogenesis of autoimmune thyroid disease (AITD). We genotyped DICER rs3742330A/G and rs1057035T/C as well as DROSHA rs644236C/T and rs10719C/T polymorphisms in 255 Hashimoto's disease (HD) patients, in 255 Graves' disease (GD) patients and in 128 healthy controls by the polymerase chain reaction (PCR)- restriction fragment length polymorphism (RFLP) method. We also examined the expression of DICER and DROSHA gene in peripheral blood mononuclear cells (PBMCs) by quantitative RT-PCR (qRT-PCR) methods. The TT genotype of the DICER rs1057035 polymorphism was less frequent in GD patients (p = 0.0098) than in healthy subjects. The CC genotype of DROSHA rs644236 polymorphism were more frequent in GD patients than in HD patients (p = 0.0171). The gene expression of DICER was lower in patients with AITD compared with that in control subjects (p = 0.0064) and was lower in patients with GD in remission than in patients with intractable GD (p = 0.0213). In addition, the expression of DROSHA was lower in patients with AITD than that in control subjects (p < 0.0001) and was lower in patients with severe HD than in patients with mild HD (p = 0.0440). In conclusion, the DICER rs1057035 TT genotype and DROSHA rs644236 CC genotype were associated with the development of GD and the differentiation between GD and HD, respectively. The expression levels of DICER and DROSHA genes were low in AITD and differed depending on the intractability of GD and the severity of HD, respectively.
Dicer和Drosha是RNase III酶，它们是大多数微小RNA（miRNA）生物合成所必需的。然而，尚无关于Dicer和Drosha与自身免疫性甲状腺疾病（AITD）发病机制关联的报道。我们采用聚合酶链反应（PCR）-限制性片段长度多态性（RFLP）方法，对255例桥本氏病（HD）患者、255例格雷夫斯病（GD）患者和128名健康对照者的DICER rs3742330A/G和rs1057035T/C以及DROSHA rs644236C/T和rs10719C/T多态性进行基因分型。我们还通过定量逆转录PCR（qRT-PCR）方法检测了外周血单个核细胞（PBMCs）中DICER和DROSHA基因的表达。DICER rs1057035多态性的TT基因型在GD患者中的频率低于健康受试者（p = 0.0098）。DROSHA rs644236多态性的CC基因型在GD患者中的频率高于HD患者（p = 0.0171）。与对照受试者相比，AITD患者中DICER的基因表达较低（p = 0.0064），缓解期GD患者的DICER表达低于难治性GD患者（p = 0.0213）。此外，AITD患者中DROSHA的表达低于对照受试者（p < 0.0001），重度HD患者的DROSHA表达低于轻度HD患者（p = 0.0440）。总之，DICER rs1057035 TT基因型和DROSHA rs644236 CC基因型分别与GD的发生以及GD和HD的鉴别有关。DICER和DROSHA基因的表达水平在AITD中较低，并且分别因GD的难治性和HD的严重程度而异。
