X-Linked miRNAs Associated with Gender Differences in Rheumatoid Arthritis

Abstract

Rheumatoid arthritis (RA) is an autoimmune disease that predominantly affects women. MicroRNAs have emerged as crucial regulators of the immune system, whose expression is deregulated in RA. We aimed at quantifying the expression level of 14 miRNAs located on the X chromosome and at identifying whether differences are associated with disease and/or sex. A case–control study of 21 RA patients and 22 age- and sex-matched healthy controls was performed on peripheral blood mononuclear cells. The expression level of five miRNAs (miR-221, miR-222, miR-532, miR-106a, and miR-98) was significantly different between RA and controls when stratifying by sex, and the expression level of four miRNAs (miR-222, miR-532, miR-98, and miR-92a) was significantly different between RA females and males. The expression quantitative trait loci (eQTL) analysis revealed a significant gender effect of the FoxP3 promoter polymorphism rs3761548A/C on miR-221, miR-222 and miR-532 expression levels, and of the FoxP3 polymorphism rs2232365A/G on miR-221 expression levels in PBMC of RA patients. These data further support the involvement of the X chromosome in RA susceptibility. X-linked miRNAs, in the context of sex differences, might provide novel insight into new molecular mechanisms and potential therapeutic targets in RA for disease treatment and prevention.

Global exosome transcriptome profiling reveals biomarkers for multiple sclerosis

“…In this regard, we have previously reported on the critical role of miR‐301a as an endogenous regulator of Th17 development in an animal model of MS . miR‐532 has also been reported to be expressed by PBMCs and to be linked to gender differences in rheumatoid arthritis susceptibility . miR‐532‐5p expression in MS PBMCs has been found to be downregulated during interferon‐β treatment .…”

“…[30][31][32] miR-301a presence has been related to various immune and autoaggressive conditions, including MS. 7,[33][34][35][36][37] In this regard, we have previously reported on the critical role of miR-301a as an endogenous regulator of Th17 development in an animal model of MS. 7 miR-532 has also been reported to be expressed by PBMCs and to be linked to gender differences in rheumatoid arthritis susceptibility. 38 miR-532-5p expression in MS PBMCs has been found to be downregulated during interferon-b treatment. 39 All of these data suggest an immune-related context of action for these 3 exosomal miRNAs, highlighted by our analysis.…”

Epigenetic Regulation Mediated by microRNAs in the Susceptibility and Pathogenesis of Rheumatoid Arthritis

“…What's more, show differential expression not only between healthy individuals and RA patients, but also between RA patients and osteoarthritis (OA), SLE, or Graves patients . Other differentially expressed miRNAs in RA patients serum include miR-4634, miR-181d, miR-3926, miR-3926, miR-9-5p, miR-219-2-3p6, miR-221, miR-222, miR-532, miR-106a, and miR-987, which highlights their potential as RA-specific diagnostic markers Khalifa et al, 2016).…”

Epigenetic Regulation Mediated by miRNA in the Susceptibility and Pathogenesis of Rheumatoid Arthritis

“…miR-122-3p, miR-3925-3p, miR-342-3p and miR-4764-5p are differentially expressed not only in healthy individuals and RA patients, but also in RA patients and OA, SLE, and Graves patients (85). What's more, miR-4634, miR-181d, miR-3926, miR-3926, miR-9-5p, miR-219-2-3p6, miR-221, miR-222, miR-532, miR-106a and miR-987 are also expressed differentially in the serum of RA patients which can be used as RA-specific diagnostic markers (85,86).…”