Elsevier

Autoimmunity Reviews

Volume 11, Issue 9, July 2012, Pages 636-641
Autoimmunity Reviews

Review
miRNAs and related polymorphisms in rheumatoid arthritis susceptibility

https://doi.org/10.1016/j.autrev.2011.11.004Get rights and content

Abstract

The epigenetic mechanisms in regulation of genes’ expression seem to be another field of research that gains land in genetic association studies of rheumatoid arthritis (RA) susceptibility factors. Recently, a new class of molecules has been discovered, the microRNAs (miRNAs). miRNAs are related to post-transcriptional regulation of genes’ expression. Different expression patterns of mir-146a, miRNA-155, miRNA-124a, mir-203, mir-223, mir-346, mir-132, mir-363, mir-498, mir-15a, and mir-16 were documented in several tissue sample types of RA patients. The polymorphisms of these miRNAs and their gene targets, which previously have been associated with RA or other autoimmune diseases, are also reviewed. Finally, using web-based tools we propose polymorphisms of the discussed miRNAs and their gene-targets that worth to be studied for their role in RA predisposition.

Section snippets

General overview

Rheumatoid arthritis (RA) is a chronic inflammatory disorder in which hypertrophy, hyperplasia and angiogenesis of synovial tissue contribute to inflammatory joint destruction [1], [2]. Both genetic and environmental factors have been implicated in RA susceptibility [3]. The main genetic factor for RA is the HLA-DRB1 gene but the HLA (human leukocyte antigen) genes account only for the one third of the genetic liability to the disease [4]. Therefore, in the recent years many other non-HLA genes

mir-146a

Increased expression of miRNA-146a has been documented in fibroblast-like synoviocytes (FLS), synovial fluid (SF), CD4 + T cells (lymphocytes positive for the CD4 phenotypic marker) from peripheral blood and synovial fluid, peripheral blood mononuclear cells (PBMC), and in serum plasma [23], [24], [25], [26], [27], [28]. Furthermore, in RA patients miRNA-146a levels in synovial fluid were lower than these of their plasma [27].

Two known gene targets of miR-146a are the TNF receptor-associated

Searching for polymorphisms associated with RA

Today, many single nucleotide polymorphisms (SNPs) in 3’-UTRs are known to alter the binding of a miRNA to its gene target causing several human diseases [75]. For this reason many web-based tools are now available for the prediction of miRNAs’ gene targets and for the identification of SNPs located in such 3’-UTR sequences. Since the interplay between SNPs and miRNAs is important, prediction of SNPs that could alter the expression of a miRNA or its complementarity with the gene target, and as

Future perspectives

The target–prediction computational tools are based mainly on the complementarity between miRNA seed-gene target and the cross-species conservation of the seed. However, the complementarity between the miRNA and its target gene can be affect by the molecular structure of miRNAs and mRNA targets, other nearby genetic variants, while the prediction of the correct pair of a miRNA and its gene target for their study in a specific disease susceptibility can be affect by the expression patterns of

Conflict of interest

The authors have no conflict of interest to report.

Take-home messages

  • There are miRNAs that are expressed differentially in tissues obtained from RA patients.

  • Polymorphisms in these miRNAs or their gene targets that affect miRNA expression levels or the correct binding among miRNA-gene target could be associated with RA susceptibility.

  • Web-based tools are now available to predict such polymorphisms that worth to be included in RA genetic association studies.

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