Methylation differences at the HLA-DRBI locus in CD4+T-Cells are associated with multiple sclerosis
Methylation differences at the HLA-DRBI locus in CD4+T-Cells are associated with multiple sclerosis
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DOI：
10.1177/1352458513516529
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发表时间：
2014-07-01
影响因子：
5.8
通讯作者：
Lechner-Scott, J.
中科院分区：
文献类型：
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作者：
Graves, M. C.;Benton, M.;Lechner-Scott, J.
背景：多发性硬化症（MS）被认为是由t细胞介导的自身免疫功能障碍引起的。发生多发性硬化症的风险受环境和遗传因素的影响。DNA甲基化的可改变差异被认为是MS风险的表观遗传因素，并可能在环境暴露和遗传遗传系统之间提供有价值的联系。目的和方法：为了确定与MS相关的甲基化变化，我们使用Illumina 450K甲基化阵列对30名复发缓解型MS患者和28名健康对照者的CD4+ T细胞进行了全基因组DNA甲基化分析。结果：在chr观察到显著的差异甲基化信号。6p2 I，在HLA-DRBI处有峰值信号。在确定优先级后，我们在该队列中确定了74个与多发性硬化相关的CpGs。最值得注意的是，我们发现了CpG岛对MS病例DRBI的主要影响(p（FDR) < 3 × 10(-3)）。此外，我们发现55个非hla CpGs表现出不同的甲基化，其中许多定位于先前与MS相关的基因。结论：我们的发现提供了HLA-DRBI DNA甲基化与MS风险相关的第一个证据。现在需要进一步的研究来验证和理解这些发现是如何参与MS病理的。
Background: Multiple sclerosis (MS) is thought to be caused by T-cell mediated autoimmune dysfunction. Risk of developing MS is influenced by environmental and genetic factors. Modifiable differences in DNA methylation are recognized as epigenetic contributors to MS risk and may provide a valuable link between environmental exposure and inherited genetic systems.Objectives and methods: To identify methylation changes associated with MS, we performed a genome-wide DNA methylation analysis of CD4+ T cells from 30 patients with relapsing remitting MS and 28 healthy controls using Illumina 450K methylation arrays.Results: A striking differential methylation signal was observed at chr. 6p2 I, with a peak signal at HLA-DRBI. After prioritisation, we identified a panel of 74 CpGs associated with MS in this cohort. Most notably we found evidence of a major effect CpG island in DRBI in MS cases (p(FDR) < 3 x 10(-3)). In addition, we found 55 non-HLA CpGs that exhibited differential methylation, many of which localise to genes previously linked to MS.Conclusions: Our findings provide the first evidence for association of DNA nnethylation at HLA-DRBI in relation to MS risk. Further studies are now warranted to validate and understand how these findings are involved in MS pathology.