Hypermethylation of MIR21 in CD4+ T cells from patients with relapsing-remitting multiple sclerosis associates with lower miRNA-21 levels and concomitant up-regulation of its target genes. (September 2018)

• Record Type: Journal Article
• Authors: Ruhrmann, Sabrina; Ewing, Ewoud; Piket, Eliane; Kular, Lara; Cetrulo Lorenzi, Julio Cesar; Fernandes, Sunjay Jude; Morikawa, Hiromasa; Aeinehband, Shahin; Sayols-Baixeras, Sergi; Aslibekyan, Stella; Absher, Devin M; Arnett, Donna K; Tegner, Jesper; Gomez-Cabrero, David; Piehl, Fredrik; Jagodic, Maja
• Is Part Of: Multiple sclerosis. Volume 24:Number 10(2018)
• Page Start: 1288
• Page End: 1300
• Publication Date: 2018-09
• Subjects: CD4+ T cells -- autoimmunity -- epigenetics -- DNA methylation -- microRNAs -- multiple sclerosis -- relapsing-remitting -- miR-21; Central nervous system -- Diseases -- Periodicals; Myelin sheath -- Diseases -- Periodicals; Inflammation -- Periodicals; Multiple sclerosis -- Periodicals; Central Nervous System Diseases -- Periodicals; Demyelinating Diseases -- Periodicals; Inflammation -- Periodicals; Multiple Sclerosis -- Periodicals; Système nerveux central -- Maladies -- Périodiques; Gaine de myéline -- Maladies -- Périodiques; Inflammation (Pathologie) -- Périodiques; Sclérose en plaques -- Périodiques; Electronic journals; 616.834005
• DOI: 10.1177/1352458517721356
• Languages: English
• ISSNs: 1352-4585

Abstract

Background: Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system caused by genetic and environmental factors. DNA methylation, an epigenetic mechanism that controls genome activity, may provide a link between genetic and environmental risk factors. Objective: We sought to identify DNA methylation changes in CD4+ T cells in patients with relapsing-remitting (RR-MS) and secondary-progressive (SP-MS) disease and healthy controls (HC). Methods: We performed DNA methylation analysis in CD4+ T cells from RR-MS, SP-MS, and HC and associated identified changes with the nearby risk allele, smoking, age, and gene expression. Results: We observed significant methylation differences in the VMP1/MIR21 locus, with RR-MS displaying higher methylation compared to SP-MS and HC. VMP1/MIR21 methylation did not correlate with a known MS risk variant in VMP1 or smoking but displayed a significant negative correlation with age and the levels of mature miR-21 in CD4+ T cells. Accordingly, RR-MS displayed lower levels of miR-21 compared to SP-MS, which might reflect differences in age between the groups, and healthy individuals and a significant enrichment of up-regulated miR-21 target genes. Conclusion: Disease-related changes in epigenetic marking of MIR21 in RR-MS lead to differences in miR-21 expression with a consequence on miR-21 target genes.