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多发性硬化症患者 CD4+T 细胞中 MIR21 的过度甲基化与 miRNA-21 水平降低以及其靶基因的伴随上调有关。

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.

机构信息

Department of Clinical Neuroscience, Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden.

Department of Clinical Neuroscience, Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden/ Department of Genetics, Medical School of Ribeirão Preto, São Paulo University, Ribeirão Preto, Brazil.

出版信息

Mult Scler. 2018 Sep;24(10):1288-1300. doi: 10.1177/1352458517721356. Epub 2017 Aug 2.

DOI:10.1177/1352458517721356
PMID:28766461
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5794671/
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.

摘要

背景

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，它可能为遗传和环境风险因素之间提供联系。

目的

我们试图确定复发缓解型（RR-MS）和继发进展型（SP-MS）疾病患者及健康对照者（HC）CD4+T 细胞中的 DNA 甲基化变化。

方法

我们对 RR-MS、SP-MS 和 HC 的 CD4+T 细胞进行了 DNA 甲基化分析，并将鉴定出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。

结果

我们观察到 VMP1/MIR21 基因座存在显著的甲基化差异，RR-MS 的甲基化水平高于 SP-MS 和 HC。VMP1/MIR21 甲基化与 VMP1 中的已知 MS 风险变体或吸烟无关，但与年龄和 CD4+T 细胞中成熟 miR-21 的水平呈显著负相关。相应地，RR-MS 与 SP-MS 和健康个体相比，miR-21 的水平较低，这可能反映了两组之间的年龄差异，以及 miR-21 靶基因的显著富集。

结论

RR-MS 中 MIR21 的表观遗传标记的疾病相关变化导致 miR-21 表达的差异，进而影响 miR-21 靶基因。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fb16/6108045/385945f3300c/10.1177_1352458517721356-fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fb16/6108045/d79142e2dbe5/10.1177_1352458517721356-fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fb16/6108045/c6b9e3e38719/10.1177_1352458517721356-fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fb16/6108045/a81694fc9419/10.1177_1352458517721356-fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fb16/6108045/385945f3300c/10.1177_1352458517721356-fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fb16/6108045/d79142e2dbe5/10.1177_1352458517721356-fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fb16/6108045/c6b9e3e38719/10.1177_1352458517721356-fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fb16/6108045/a81694fc9419/10.1177_1352458517721356-fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fb16/6108045/385945f3300c/10.1177_1352458517721356-fig4.jpg

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