Polymorphisms in MIR499A and MIR125A gene are associated with autoimmune thyroid diseases

Abstract

Background: Single nucleotide polymorphisms (SNPs) of the miR-146a, miR-499a and miR-125a have been shown to be associated with the susceptibility to several autoimmune diseases. This study was conducted to identify the association of SNPs rs2910164, rs57095329, rs3746444 and rs12976445 with autoimmune thyroid diseases (AITDs) in a Chinese Han population.

Methods: We enrolled 1061 patients with AITDs, including 701 patients with Graves' disease (GD) and 360 patients with Hashimoto's thyroiditis (HT), and 938 healthy individuals for a case-control genetic association study. Four SNPs were selected for genotyping by multiplex polymerase chain reaction and ligase detection reaction.

Results: The frequencies of rs3746444 genotypes in patients with AITD and GD differed significantly from those in the controls. The frequencies of rs12976445 genotypes in patients with HT differed significantly from those in the controls. The frequencies of allele C in HT groups were significantly higher than those in control group. For the rs3746444 polymorphism, genetic associations between the combinational genotype and AITD/GD risk were observed in the dominant model, recessive model, and overdominant model. For the rs12976445 polymorphism, genetic associations between the combinational genotype and HT risk were also found in the dominant model and overdominant model. Moreover, gene-sex interactions were identified by GMDR and 2 × 2 crossover analysis.

Conclusions: Our results suggest rs3746444 (miR-499a) and rs12976445 (miR-125a) associated with AITD susceptibility and potential gene-sex interactions between the four polymorphisms and AITD.

Keywords: Autoimmune thyroid diseases (AITD); Graves' disease (GD); Hashimoto's thyroiditis (HT); MicroRNAs; Single nucleotide polymorphism (SNP).