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Expression and Genetic Analysis of MicroRNAs Involved in Multiple Sclerosis
Department of Pathophysiology and Transplantation, "Dino Ferrari" Center, University of Milan, IRCCS Ospedale Maggiore Policlinico, Via F.Sforza 35, 20122 Milan, Italy
Department of Neuroscience, Azienda Ospedaliera Città della Salute e della Scienza di Torino, Corso Bramante 88, 10126 Turin, Italy
* Author to whom correspondence should be addressed.
Received: 5 December 2012; in revised form: 19 February 2013 / Accepted: 20 February 2013 / Published: 25 February 2013
Abstract: Evidence underlines the importance of microRNAs (miRNAs) in the pathogenesis of multiple sclerosis (MS). Based on the fact that miRNAs are present in human biological fluids, we previously showed that miR-223, miR-23a and miR-15b levels were downregulated in the sera of MS patients versus controls. Here, the expression levels of these candidate miRNAs were determined in peripheral blood mononuclear cells (PBMCs) and the serum of MS patients, in addition to three genotyped single nucleotide polymorphisms (SNPs). Mapping in the genomic regions of miR-223, miR-23a and miR-15b genes, 399 cases and 420 controls were tested. Expression levels of miR-223 and miR-23a were altered in PBMCs from MS patients versus controls. Conversely, there were no differences in the expression levels of miR-15b. A significantly decreased genotypic frequency of miR-223 rs1044165 T/T genotype was observed in MS patients. Moreover, the allelic frequency of miR-23a rs3745453 C allele was significantly increased in patients versus controls. In contrast, there were no differences in the distribution of miR-15b SNP. In conclusion, our results suggest that miR-223 and miR-23a could play a role in the pathogenesis of MS. Moreover, miR-223 rs1044165 polymorphism likely acts as a protective factor, while miR-23a rs3745453 variant seems to act as a risk factor for MS.
Keywords: multiple sclerosis; microRNA; gene expression; association analysis
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Ridolfi, E.; Fenoglio, C.; Cantoni, C.; Calvi, A.; De Riz, M.; Pietroboni, A.; Villa, C.; Serpente, M.; Bonsi, R.; Vercellino, M.; Cavalla, P.; Galimberti, D.; Scarpini, E. Expression and Genetic Analysis of MicroRNAs Involved in Multiple Sclerosis. Int. J. Mol. Sci. 2013, 14, 4375-4384.
Ridolfi E, Fenoglio C, Cantoni C, Calvi A, De Riz M, Pietroboni A, Villa C, Serpente M, Bonsi R, Vercellino M, Cavalla P, Galimberti D, Scarpini E. Expression and Genetic Analysis of MicroRNAs Involved in Multiple Sclerosis. International Journal of Molecular Sciences. 2013; 14(3):4375-4384.
Ridolfi, Elisa; Fenoglio, Chiara; Cantoni, Claudia; Calvi, Alberto; De Riz, Milena; Pietroboni, Anna; Villa, Chiara; Serpente, Maria; Bonsi, Rossana; Vercellino, Marco; Cavalla, Paola; Galimberti, Daniela; Scarpini, Elio. 2013. "Expression and Genetic Analysis of MicroRNAs Involved in Multiple Sclerosis." Int. J. Mol. Sci. 14, no. 3: 4375-4384.