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Int. J. Mol. Sci. 2016, 17(11), 1852;

X-Linked miRNAs Associated with Gender Differences in Rheumatoid Arthritis

Inserm, U1183, Institute for Regenerative Medicine and Biotherapies, CHU Saint Eloi, 80 Avenue Augustin Fliche, 34295 Montpellier, France
University of Montpellier, Boulevard Henri IV, 34090 Montpellier, France
Clinical Department for Osteoarticular Diseases and Biotherapy, University Hospital Lapeyronie, 34295 Montpellier, France
Inserm, U1051, Institute for Neurosciences Montpellier, CHU Saint Eloi, 80 Avenue Augustin Fliche, 34295 Montpellier, France
Author to whom correspondence should be addressed.
Academic Editor: Martin Pichler
Received: 22 August 2016 / Revised: 17 October 2016 / Accepted: 31 October 2016 / Published: 8 November 2016
(This article belongs to the Collection Regulation by Non-Coding RNAs)
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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. View Full-Text
Keywords: rheumatoid arthritis; miRNA; gender; X-chromosome; FoxP3 rheumatoid arthritis; miRNA; gender; X-chromosome; FoxP3

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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

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Khalifa, O.; Pers, Y.-M.; Ferreira, R.; Sénéchal, A.; Jorgensen, C.; Apparailly, F.; Duroux-Richard, I. X-Linked miRNAs Associated with Gender Differences in Rheumatoid Arthritis. Int. J. Mol. Sci. 2016, 17, 1852.

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