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

Sabrina Ruhrmann, Ewoud Ewing, Eliane Piket, Lara Kular, Julio Cesar Cetrulo Lorenzi, Sunjay Jude Fernandes, Hiromasa Morikawa, Shahin Aeinehband, Sergi Sayols-Baixeras, Stella Aslibekyan, Devin M Absher, Donna K Arnett, Jesper Tegner, David Gomez Cabrero Lopez, Fredrik Piehl, Maja Jagodic

Research output: Contribution to journalArticlepeer-review

32 Citations (Scopus)
156 Downloads (Pure)

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.

Original languageEnglish
Number of pages13
JournalMultiple sclerosis (Houndmills, Basingstoke, England)
Early online date2 Aug 2017
DOIs
Publication statusE-pub ahead of print - 2 Aug 2017

Fingerprint

Dive into the research topics of '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'. Together they form a unique fingerprint.

Cite this