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Genetic Association and Altered Gene Expression of Mir-155 in Multiple Sclerosis Patients
Dipartimento di Biologia e Genetica per le Scienze Mediche, Università degli Studi di Milano, Milano, Italia/Via Viotti 3/5, Milan 20133, Italy
Hemostasis & Thrombosis Center, Hematology Section and Department Biomedical Sciences & Advanced Therapies, University of Ferrara, Ferrara, Italy/Corso Giovecca 203, Ferrara 44121, Italy
Department of Neurological, Neuropsychological, Morphological and Movement Sciences, Policlinico G. Rossi, University of Verona, Verona, Italy/Piazzale L.A. Scuro 10,Verona 37134, Italy
Department of Medical Sciences, University of Eastern Piedmont, Novara, Italy/Via Solaroli, 17, Novara 28100, Italy
Interdisciplinary Research Center of Autoimmune Diseases (IRCAD), University of Eastern Piedmont, Novara, Italy/Via Solaroli, 17, Novara 28100, Italy
Department of Neurology, A.O.U. Maggiore della Carità, Novara, Italy/Corso Mazzini 18, Novara 28100, Italy
* Author to whom correspondence should be addressed.
Received: 19 September 2011; in revised form: 31 October 2011 / Accepted: 22 November 2011 / Published: 1 December 2011
Abstract: Multiple sclerosis (MS) is a complex autoimmune disease of the central nervous system characterized by chronic inflammation, demyelination, and axonal damage. As microRNA (miRNA)-dependent alterations in gene expression in hematopoietic cells are critical for mounting an appropriate immune response, miRNA deregulation may result in defects in immune tolerance. In this frame, we sought to explore the possible involvement of miRNAs in MS pathogenesis by monitoring the differential expression of 22 immunity-related miRNAs in peripheral blood mononuclear cells of MS patients and healthy controls, by using a microbead-based technology. Three miRNAs resulted >2 folds up-regulated in MS vs controls, whereas none resulted down-regulated. Interestingly, the most up-regulated miRNA (mir-155; fold change = 3.30; P = 0.013) was previously reported to be up-regulated also in MS brain lesions. Mir-155 up-regulation was confirmed by qPCR experiments. The role of mir-155 in MS susceptibility was also investigated by genotyping four single nucleotide polymorphisms (SNPs) mapping in the mir-155 genomic region. A haplotype of three SNPs, corresponding to a 12-kb region encompassing the last exon of BIC (the B-cell Integration Cluster non-coding RNA, from which mir-155 is processed), resulted associated with the disease status (P = 0.035; OR = 1.36, 95% CI = 1.05–1.77), suggesting that this locus strongly deserves further investigations.
Keywords: multiple sclerosis; miRNA; expression profile; mir-155; association analysis
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Paraboschi, E.M.; Soldà, G.; Gemmati, D.; Orioli, E.; Zeri, G.; Benedetti, M.D.; Salviati, A.; Barizzone, N.; Leone, M.; Duga, S.; Asselta, R. Genetic Association and Altered Gene Expression of Mir-155 in Multiple Sclerosis Patients. Int. J. Mol. Sci. 2011, 12, 8695-8712.
Paraboschi EM, Soldà G, Gemmati D, Orioli E, Zeri G, Benedetti MD, Salviati A, Barizzone N, Leone M, Duga S, Asselta R. Genetic Association and Altered Gene Expression of Mir-155 in Multiple Sclerosis Patients. International Journal of Molecular Sciences. 2011; 12(12):8695-8712.
Paraboschi, Elvezia Maria; Soldà, Giulia; Gemmati, Donato; Orioli, Elisa; Zeri, Giulia; Benedetti, Maria Donata; Salviati, Alessandro; Barizzone, Nadia; Leone, Maurizio; Duga, Stefano; Asselta, Rosanna. 2011. "Genetic Association and Altered Gene Expression of Mir-155 in Multiple Sclerosis Patients." Int. J. Mol. Sci. 12, no. 12: 8695-8712.