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.
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.
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DOI：
10.1177/1352458517721356
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发表时间：
2018-09
期刊：
影响因子：
--
通讯作者：
Jagodic M
中科院分区：
文献类型：
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作者：
Ruhrmann S;Ewing E;Piket E;Kular L;Cetrulo Lorenzi JC;Fernandes SJ;Morikawa H;Aeinehband S;Sayols-Baixeras S;Aslibekyan S;Absher DM;Arnett DK;Tegner J;Gomez-Cabrero D;Piehl F;Jagodic M
多发性硬化症（MS）是一种由遗传和环境因素引起的中枢神经系统慢性炎症性疾病。 DNA 甲基化是一种控制基因组活性的表观遗传机制，可能提供遗传和环境风险因素之间的联系。我们试图鉴定复发缓解型 (RR-MS) 和继发进展型 (SP-MS) 疾病患者以及健康对照 (HC) 患者 CD4+ T 细胞中 DNA 甲基化的变化。我们对来自 RR-MS、SP-MS 和 HC 的 CD4+ T 细胞进行 DNA 甲基化分析，并将确定的变化与附近的风险等位基因、吸烟、年龄和基因表达相关联。我们观察到 VMP1/MIR21 位点的显着甲基化差异，与 SP-MS 和 HC 相比，RR-MS 显示出更高的甲基化程度。 VMP1/MIR21 甲基化与 VMP1 中已知的 MS 风险变异或吸烟无关，但与年龄和 CD4+ T 细胞中成熟 miR-21 的水平呈显着负相关。因此，与 SP-MS 相比，RR-MS 显示出较低水平的 miR-21，这可能反映了各组和健康个体之间的年龄差异以及上调的 miR-21 靶基因的显着富集。 RR-MS 中 MIR21 表观遗传标记的疾病相关变化导致 miR-21 表达差异，从而影响 miR-21 靶基因。
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. 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). 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. 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. 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.
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影响因子：
4.8
作者：
Devlin, Cecilia M.;Lahm, Tim;Petrache, Irina
通讯作者：
Petrache, Irina
影响因子：
9.8
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Huehn J
影响因子：
2.6
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Aslibekyan S;Kabagambe EK;Irvin MR;Straka RJ;Borecki IB;Tiwari HK;Tsai MY;Hopkins PN;Shen J;Lai CQ;Ordovas JM;Arnett DK
通讯作者：
Arnett DK
影响因子：
4.6
作者：
Muñoz-Culla M;Irizar H;Sáenz-Cuesta M;Castillo-Triviño T;Osorio-Querejeta I;Sepúlveda L;López de Munain A;Olascoaga J;Otaegui D
通讯作者：
Otaegui D
影响因子：
46.9
作者：
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