Significance of Polymorphism and Expression of miR-146a and NFkB1 Genetic Variants in Patients with Rheumatoid Arthritis

AbstractMicroRNA-146a (miR-146a) has been shown to play an important role in the regulation of inflammatory innate immune responses, and found to be differentially expressed in rheumatoid arthritis (RA). Through NF- κB pathway, this molecule is able to stimulate the release of pro-inflammatory cytokines such as TNF-α, IL-1β, and IL-17. It has been also suggested that single-nucleotide polymorphisms (SNPs) in miRNA sequences may alter miRNA expression and that miR-146a rs2910164 SNP may contribute to RA devel opment. These observations prompted us to analyze the potential associations between themiR-146a-3p (rs2910164, G  >  C) andNFkB1 (rs28362491, ins/del ATTG) polymorphisms and miR-146a-5p expression in patients ’ sera in relation to clinical outcome of the treatment as well as predisposition to RA. Genotyping was performed in 111 patients and 130 healthy individuals while 16 controls and 13 RA patients (before and after three months of therapy with TNF-α inhibitors (TNFi)) were studied for the circulati ng miR-146a-5p serum expression level. Patients carrying theNFkB1 ins/ins genotype were characterized by worse response to TNFi treatment (p = 0.023). In patients, before TNFi therapy, expression levels of miR-146a-5p were less (0.422 ± 0.171) as compared to those detected after three months of treatment (1.809 ± 0.658,p = 0.033) and observed for healthy controls (5.302 ± 2.112,p = 0.048). Moreover, patients with higher circulating miR-146a-5p leve...
Source: Archivum Immunologiae et Therapiae Experimentalis - Category: Allergy & Immunology Source Type: research