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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.

SUBMITTER: Khalifa O

PROVIDER: S-EPMC5133852 | biostudies-literature | 2016 Nov

REPOSITORIES: biostudies-literature

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X-Linked miRNAs Associated with Gender Differences in Rheumatoid Arthritis.

Khalifa Olfa O Pers Yves-Marie YM Ferreira Rosanna R Sénéchal Audrey A Jorgensen Christian C Apparailly Florence F Duroux-Richard Isabelle I

International journal of molecular sciences 20161108 11

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 exp ...[more]

PMID: 27834806

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Project description:Rheumatoid arthritis (RA) is a systemic autoimmune disease with severe joint inflammation and destruction associated with an inflammatory environment. The etiology behind RA remains to be elucidated; most updated concepts include the participation of environmental, proteomic, epigenetic, and genetic factors. Epigenetic is considered the missing link to explain genetic diversification among RA patients. Within epigenetic factors participating in RA, miRNAs are defined as small noncoding molecules with a length of approximately 22 nucleotides, capable of gene expression modulation, either negatively through inhibition of translation and degradation of the mRNA or positively through increasing the translation rate. Over the last decade and due to the feasibility of the identification of miRNAs among different tissues and compartments, they have been proposed as biomarkers for diagnosis, prognosis, and response to treatment in different pathologies. Nevertheless, miRNAs seem to be important regulators of networks instead of single genes; their hypothetical use as biomarkers needs to rely on a functional integrative description of their effects in the biological process of autoimmune conditions which until now is missing. Therefore, we underwent a bibliographic search for review and original articles related to miRNAs and their possible implications in rheumatoid arthritis. We found 48 different studies using the key words "miRNAs" or "micro-RNAs" and "rheumatoid arthritis" with restriction of publication dates from 2011 to 2016, in humans, using the English language. After a critical reading, we provide in this paper a functional view with respect to miRNA biogenesis, interaction with targets that are expressed in specific cells and tissues, during different stages of inflammatory responses associated with RA, and recognized specific areas where miRNAs might also have a pathogenic role but remain undescribed. Our results will be useful in designing future research projects that can support miRNAs as biomarkers or therapeutic targets in RA.

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X-Linked miRNAs Associated with Gender Differences in Rheumatoid Arthritis.

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X-Linked miRNAs Associated with Gender Differences in Rheumatoid Arthritis.

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