Associations of single nucleotide polymorphisms in precursor‐microRNA (miR)‐125a and the expression of mature mi R ‐125a with the development and prognosis of autoimmune thyroid diseases

Summary It is important to search the biomarker to predict the development and prognosis of autoimmune thyroid diseases ( AITD s) such as H ashimoto's disease ( HD ) and G raves' disease ( GD ). MicroRNA (mi R ) bind directly to the 3′ untranslated region of specific target m RNA s to suppress the expression of proteins, promote the degradation of target m RNA s and regulate immune response. mi R ‐125a is known to be a negative regulator of regulated upon activation normal T cell expressed and secreted ( RANTES ), interleukin ( IL )‐6 and transforming growth factor ( TGF )‐β; however, its association with AITDs remains unknown. To clarify the association between AITD s and miR ‐125a, we genotyped the rs12976445 C / T , rs10404453 A / G and rs12975333 G / T polymorphisms in the MIR 125 A gene, which encodes mi R ‐125a, using direct sequencing and polymerase chain reaction–restriction fragment length polymorphism (PC R–RFLP ) methods in 155 patients with GD , 151 patients with HD and 118 healthy volunteers. We also examined the expression of mi R ‐125a in peripheral blood mononuclear cells ( PBMC s) from 55 patients with GD , 79 patients with HD and 38 healthy volunteers using quantitative real‐time PCR methods. We determined that the CC genotype and C allele of the rs12976445 C / T polymorphism were significantly more frequent in patients with HD compared with control subjects ( P  < 0·05) and in intractable GD compared with GD in remission ( P  < 0·05). The expression of mi R ‐125a was correlated negatively with age ( P  = 0·0010) and down‐regulated in patients with GD compared with control subjects ( P  = 0.0249). In conclusion, mi R ‐125a expression in PBMC s and the rs12976445 C / T polymorphism were associated with AITD development and prognosis.