DICER and DROSHA gene expression and polymorphisms in autoimmune thyroid diseases

Abstract

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.

Keywords: Dicer; Drosha; autoimmune thyroid disease; severity; single nucleotide polymorphism.