文献简介

出版社:genetics

作  者:Devin M. Absher1, Xinrui Li, Lindsay L. Waite, Andrew Gibson, Kevin Roberts, Jeffrey Edberg, W. Winn Chatham, Robert P. Kimberly

编  号:

关键字:

年  份:2013   点击量:809

文献摘要

Systemic lupus erythematosus (SLE) is an autoimmune disease with known genetic, epigenetic, and environmental risk factors. To assess the role of DNA methylation in SLE, we collected CD4+ T-cells, CD19+ B-cells, and CD14+ monocytes from 49 SLE patients and 58 controls, and performed genome-wide DNA methylation analysis with Illumina Methylation450 microarrays. 

系统性红斑狼疮(SLE)是一种与已知遗传因素、表观因素和环境危险因素有关的自身免疫性疾病。为了评估SLEDNA甲基化的作用,我们收集了49SLE患者和58名对照组的CD4 + T细胞、CD19+ B细胞和CD14+单核细胞,并应用Illumina甲基化450基因芯片对全基因组DNA甲基化进行分析。

 

We identified 166 CpGs in B-cells, 97 CpGs in monocytes, and 1,033 CpGs in T-cells with highly significant changes in DNA methylation levels (p<1×10-8) among SLE patients. Common to all three cell-types were widespread and severe hypomethylation events near genes involved in interferon signaling (type I). 

SLE患者中,我们发现B细胞中有166 CpGs,单核细胞中有97CpGsT-细胞中有1033CpGsSLE患者中这些细胞的DNA甲基化水平有高度显著的差异(p<1×10-8)。三种类型的细胞分布广泛,并且在基因上发生严重地低甲基化涉及干扰素转导信号(I型)。

 

These interferon-related changes were apparent in patients collected during active and quiescent stages of the disease, suggesting that epigenetically-mediated hypersensitivity to interferon persists beyond acute stages of the disease and is independent of circulating interferon levels. This interferon hypersensitivity was apparent in memory, naive and regulatory T-cells, suggesting that this epigenetic state in lupus patients is established in progenitor cell populations.

在疾病的活动期和静止期,患者的干扰素相关变化较明显,这表明表观遗传介导的干扰素超敏反应持续超出该病的急性期,并且不依赖于循环干扰素水平。这种干扰素超敏反应在记忆性、先天性和调节性T细胞中较明显,提示红斑狼疮患者的这种表观遗传发生于前体细胞群。

 

We also identified a widespread, butlower amplitude shift in methylation in CD4+T-cells (>16,000 CpGs at FDR<1%) near genes involved in cell division and MAPK signaling. These cell type-specific effects are consistent with disease-specific changes in the composition of the CD4+ population and suggest that shifts in the proportion of CD4+ subtypes can be monitored at CpGs with subtype-specific DNA methylation patterns.

我们还发现在CD4+T细胞中,与细胞分裂和MAPK信号转导相关基因附近有低幅度的甲基化转移(>16,000 CpGs at FDR<1%)。这些细胞类型特异性的结果是与由与疾病特异性的CD4+细胞群构成变化相一致的,表明CD4+亚型比例的改变可以被亚型特异性DNA甲基化模式的CpGs监测。