Expression and genetic analysis of miRNAs involved in CD4+ cell activation in patients with multiple sclerosis

• Published in: Neuroscience letters 2011-10, Vol.504 (1), p.9-12
• Main Authors: Fenoglio, Chiara, Cantoni, Claudia, De Riz, Milena, Ridolfi, Elisa, Cortini, Francesca, Serpente, Maria, Villa, Chiara, Comi, Cristoforo, Monaco, Francesco, Mellesi, Luisa, Valzelli, Stefano, Bresolin, Nereo, Galimberti, Daniela, Scarpini, Elio
• Format: Article
• Language: English
• Subjects: Adult; Biological and medical sciences; Case-Control Studies; CD4; CD4-Positive T-Lymphocytes; Cohort Studies; Female; Fundamental and applied biological sciences. Psychology; Gene Expression; Genetic Association Studies; Humans; Immune system; Leukocytes, Mononuclear - metabolism; Lymphocyte Activation - genetics; Male; MicroRNAs - genetics; MicroRNAs - physiology; Middle Aged; miRNA; Multiple sclerosis; Multiple Sclerosis, Relapsing-Remitting - genetics; Polymorphism, Single Nucleotide; Risk factor; Vertebrates: nervous system and sense organs
• ISSN: 0304-3940; 1872-7972
• DOI: 10.1016/j.neulet.2011.08.021

► Increased expression of miR-21, miR-146a and-b was observed in (RR)MS patients. ► SP- and PPMS patients have a miRNA profile similar to controls. ► No differences in the frequencies of rs2910164 was found between patients and controls. ► miRNA dysregulation may contribute to the pathogenesis of MS. MicroRNA (miRNA)-mediate RNA interference has been identified as a novel mechanism that regulates protein expression. It is recognised that miRNAs play essential roles in the immune system and for correct function in the brain. Moreover, it is now clear that abnormal miRNA expression is a common feature of several diseases involving the immune system including multiple sclerosis (MS). Expression analysis for miR-21, miR-146a and -b, miR-150, miR-155 was carried out in peripheral mononuclear cells (PBMC) from a cohort of 29 MS patients and 19 controls. Subsequently, a case control study for miR-146 rs2910164 variant was performed in an overall population of 346 MS cases and 339 controls. A statistically significant increased expression of miR-21, miR-146a and -b was observed in relapsing remitting (RR)MS patients as compared with controls (1.44 ± 0.13 vs 0.79 ± 0.06, P = 0.036; 1.50 ± 0.12 vs 0.84 ± 0.08, P = 0.039; 1.54 ± 0.15 vs 0.72 ± 0.08, P = 0.001 respectively). On the contrary, no differences were found in the expression levels of both miR-150 and miR-155 in patients as compared with controls ( P > 0.05). The genetic association study failed to find any differences in the frequencies of rs2910164 between patients and controls. miRNA dysregulation may contribute to the pathogenesis of MS and highlights the possibility to define different disease entities with specific miRNAs profile.