title: Significance of Polymorphism and Expression of miR-146a and NFkB1 Genetic Variants in Patients with Rheumatoid Arthritis.
abstract: MicroRNA-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 development. These observations prompted us to analyze the potential associations between the miR-146a-3p (rs2910164, G > C) and NFkB1 (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 circulating miR-146a-5p serum expression level. Patients carrying the NFkB1 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 levels after three months of TNFi administration were more frequently carrying the rs2910164-C allele (p = 0.032). These results support the hypothesis that miR-146a might be involved in pathogenesis of RA and imply that miR-146a-3p polymorphism may be associated with miR-146a-5p levels in serum after anti-TNF-α treatment.
authors.affiliation: Laboratory of Clinical Immunogenetics and Pharmacogenetics, Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wroclaw, Poland.|Department of Internal, Occupational Diseases, Hypertension and Clinical Oncology, Wroclaw Medical University, Wroclaw, Poland.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Bogunia-Kubik
authors.affiliation: Laboratory of Clinical Immunogenetics and Pharmacogenetics, Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wroclaw, Poland.
authors.forename: Barbara
authors.initials: B
authors.lastname: Wysoczańska
authors.affiliation: Laboratory of Clinical Immunogenetics and Pharmacogenetics, Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wroclaw, Poland.
authors.forename: Dagmara
authors.initials: D
authors.lastname: Piątek
authors.affiliation: Laboratory of Clinical Immunogenetics and Pharmacogenetics, Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wroclaw, Poland.
authors.forename: Milena
authors.initials: M
authors.lastname: Iwaszko
authors.affiliation: Laboratory of Clinical Immunogenetics and Pharmacogenetics, Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wroclaw, Poland.|National Institute of Geriatrics Rheumatology and Rehabilitation, Warsaw, Poland.
authors.forename: Marzena
authors.initials: M
authors.lastname: Ciechomska
authors.affiliation: Department of Rheumatology and Internal Medicine, Wroclaw Medical University, Borowska 213, 50-556, Wroclaw, Poland. jurekswierkot0@poczta.onet.pl.
authors.forename: Jerzy
authors.initials: J
authors.lastname: Świerkot
mesh_terms: D000483:Alleles; D001172:Arthritis, Rheumatoid / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007113:Immunity, Innate; D007249:Inflammation; D035683:MicroRNAs / Q000235:genetics*; D052002:NF-kappa B p50 Subunit / Q000235:genetics*; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors
chemical_list: C542542:MIRN146 microRNA, human; D035683:MicroRNAs; D052002:NF-kappa B p50 Subunit; C489548:NFKB1 protein, human; C439524:TNF protein, human; D014409:Tumor Necrosis Factor-alpha
keywords: Disease susceptibility; NFkB1 polymorphism; Response to treatment; Rheumatoid arthritis; miRNA-146a-3p polymorphism; miRNA-146a-5p serum level