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Genetic Association and Altered Gene Expression of Mir-155 in Multiple Sclerosis Patients

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·International Journal of Molecular Sciences
DOI 10.3390/ijms12128695PMC PMC3257096
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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.

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Metadata

Authors
Paraboschi, E. M., Soldà, G., Gemmati, D., Orioli, E., Zeri, G., Benedetti, M. D., Salviati, A., Barizzone, N., Leone, M., Duga, S., & Asselta, R.
Venue
International Journal of Molecular Sciences
Publisher
MDPI AG
Published
2011-12-01
Volume
12
Issue
12
Pages
8695-8712
ISSN
1422-0067
DOI
10.3390/ijms12128695
PMC
PMC3257096
Cited by
102
References
8
Language
en
Licence
creativecommons.org/licenses/by/3.0/ (vor)

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