Genetic association and altered gene expression of mir-155 in multiple sclerosis patients

Elvezia Maria Paraboschi, Giulia Soldà, Donato Gemmati, Elisa Orioli, Giulia Zeri, Maria Donata Benedetti, Alessandro Salviati, Nadia Barizzone, Maurizio Leone, Stefano Duga, Rosanna Asselta

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)8695-8712
Number of pages18
JournalInternational Journal of Molecular Sciences
Volume12
Issue number12
DOIs
Publication statusPublished - Dec 2011

Keywords

  • Association analysis
  • Expression profile
  • Mir-155
  • miRNA
  • Multiple sclerosis

ASJC Scopus subject areas

  • Computer Science Applications
  • Molecular Biology
  • Catalysis
  • Inorganic Chemistry
  • Spectroscopy
  • Organic Chemistry
  • Physical and Theoretical Chemistry
  • Medicine(all)

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  • Cite this

    Paraboschi, E. M., Soldà, G., Gemmati, D., Orioli, E., Zeri, G., Benedetti, M. D., Salviati, A., Barizzone, N., Leone, M., Duga, S., & Asselta, R. (2011). Genetic association and altered gene expression of mir-155 in multiple sclerosis patients. International Journal of Molecular Sciences, 12(12), 8695-8712. https://doi.org/10.3390/ijms12128695