title: Genetic association and altered gene expression of mir-155 in multiple sclerosis patients.
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.
authors.affiliation: Dipartimento di Biologia e Genetica per le Scienze Mediche, Università Degli Studi di Milano, Milano, Italia/Via Viotti 3/5, Milan 20133, Italy. elvezia.paraboschi@unimi.it
authors.forename: Elvezia Maria
authors.initials: EM
authors.lastname: Paraboschi
authors.forename: Giulia
authors.initials: G
authors.lastname: Soldà
authors.forename: Donato
authors.initials: D
authors.lastname: Gemmati
authors.forename: Elisa
authors.initials: E
authors.lastname: Orioli
authors.forename: Giulia
authors.initials: G
authors.lastname: Zeri
authors.forename: Maria Donata
authors.initials: MD
authors.lastname: Benedetti
authors.forename: Alessandro
authors.initials: A
authors.lastname: Salviati
authors.forename: Nadia
authors.initials: N
authors.lastname: Barizzone
authors.forename: Maurizio
authors.initials: M
authors.lastname: Leone
authors.forename: Stefano
authors.initials: S
authors.lastname: Duga
authors.forename: Rosanna
authors.initials: R
authors.lastname: Asselta
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D005260:Female; D056726:Genetic Association Studies; D056426:Genetic Loci; D006239:Haplotypes; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000235:genetics* / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide; D015854:Up-Regulation
chemical_list: C524942:MIRN155 microRNA, human; D035683:MicroRNAs