TY - JOUR
T1 - 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
AU - Ruhrmann, Sabrina
AU - Ewing, Ewoud
AU - Piket, Eliane
AU - Kular, Lara
AU - Cetrulo Lorenzi, Julio Cesar
AU - Fernandes, Sunjay Jude
AU - Morikawa, Hiromasa
AU - Aeinehband, Shahin
AU - Sayols-Baixeras, Sergi
AU - Aslibekyan, Stella
AU - Absher, Devin M.
AU - Arnett, Donna K.
AU - Tegner, Jesper
AU - Gomez-Cabrero, David
AU - Piehl, Fredrik
AU - Jagodic, Maja
N1 - Publisher Copyright:
© The Author(s), 2017.
PY - 2018/9/1
Y1 - 2018/9/1
N2 - 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.
AB - 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.
KW - CD4+ T cells
KW - DNA methylation
KW - autoimmunity
KW - epigenetics
KW - miR-21
KW - microRNAs
KW - multiple sclerosis
KW - relapsing-remitting
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U2 - 10.1177/1352458517721356
DO - 10.1177/1352458517721356
M3 - Article
AN - SCOPUS:85029581966
SN - 1352-4585
VL - 24
SP - 1288
EP - 1300
JO - Multiple Sclerosis Journal
JF - Multiple Sclerosis Journal
IS - 10
ER -