Possible use of miRNAs-146a and -499 expression and their polymorphisms as diagnostic markers for rheumatoid arthritis

Abstract

Rheumatoid arthritis (RA) is a systemic autoimmune disorder affecting the peripheral joints. Different microRNAs had been investigated in RA including miRNA-146a meanwhile, miRNA-499 there were no studies to prove its expression in RA serum samples. This study was performed to investigate expression of both miRNAs-146a and -499 and their polymorphisms in Egyptian patients with RA and to evaluate their relationship with clinico-pathological data. The present study includes 108 subjects classified into two main groups: 52 RA patients and 56 unrelated healthy controls. RA patients were subclassified according to DAS28 score into inactive (23 patients) and active (29 patients). Quantitative expression of serum miRNA-146a, miRNA-499 as well as their Genotyping rs2910164 (C/G) and rs3746444 (T/C), respectively, were done to all subjects using real-time PCR. Serum miRNA-146a and -499 were significantly over expressed in RA patients, but they were not correlated to disease activity. Serum miRNA-146a was negatively correlated with anti-nuclear antibodies (ANA). miRNA-146a (rs2910164) genotyping revealed that the GG genotype and the frequency of the G allele were significantly higher in RA patients compared to the controls. miRNA-499 (rs3746444), genotyping revealed that the CC genotype and the frequency of the C allele were significantly higher. It can be concluded that both miRNAs-146a and -499 can be used as diagnostic markers for RA patients. Both miRNA-146a (rs2710164) and miRNA-499 (rs3746444) were significantly associated with RA susceptibility. The C allele of miRNA-146a (rs2710164) can be considered to be protective. On the other hand, the C allele of miRNA-499 (rs3746444) was significantly associated with RA susceptibility.