ReviewmiRNAs and related polymorphisms in rheumatoid arthritis susceptibility
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.
References (78)
- et al.
Epidemiology of adult rheumatoid arthritis
Autoimmun Rev
(2005) - et al.
Incidence and prevalence of rheumatoid arthritis, based on the 1987 American College of Rheumatology criteria: a systematic review
Semin Arthritis Rheum
(2006) Rheumatic diseases: environment and genetics
Joint Bone Spine
(2009)- et al.
Innate immunity, epigenetics and autoimmunity in rheumatoid arthritis
Mol Immunol
(2009) - et al.
Genomic DNA methylation: the mark and its mediators
Trends Biochem Sci
(2006) - et al.
Methylation-induced repression-belts, braces, and chromatin
Cell
(1999) Chromatin modifications and their function
Cell
(2007)Non-coding RNAs, epigenetics and complexity
Gene
(2008)- et al.
MicroRNAs and the skin: tiny players in the body's largest organ
J Dermatol Sci
(2009) - et al.
MicroRNA-10a binds the 5‘UTR of ribosomal protein mRNAs and enhances their translation
Mol Cell
(2008)