Department of Geriatrics, Renmin Hospital of Wuhan University, Wuhan University, Wuhan, China.
Department of Cardiology, Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan, China.
J Cell Biochem. 2019 Aug;120(8):13001-13011. doi: 10.1002/jcb.28571. Epub 2019 Mar 12.
Kawasaki disease (KD) is a childhood febrile vasculitis with unknown etiology. Epigenetic regulation in the gene expression dynamics has become increasingly important in KD. Thus, we performed an integrated analysis of DNA methylation and gene expression data to identify novel molecular mechanisms and key functional genes in KD.
DNA methylation (GSE84624) and gene expression (GSE68004) datasets were downloaded from Gene Expression Omnibus. Methylated-differentially expressed genes (mDEGs) were documented as the overlapping genes between the differentially methylated genes (DMGs) in GSE84624 and differentially expressed genes (DEGs) in GSE68004. Functional enrichment analyses of the mDEGs were conducted using DAVID database. Protein-protein interaction (PPI) network was then constructed to obtain the hub genes involved in KD using STRING database.
A total of 1389 DMGs and 1362 DEGs were screened out between KD and control samples. Overlapping of them resulted in four hypermethylated/downregulated and 187 hypomethylated/upregulated genes. These mDEGs were mainly enriched in inflammation response, innate immune response, and blood coagulation, and signaling pathways such as platelet activation, osteoclast differentiation, and chemokine signaling pathway. PPI network analyses identified MAPK14 and PHLPP1 as the hub genes involved in KD, which could distinguish KD from other common pediatric febrile diseases. In addition, the methylation and expression levels of MAPK14 and PHLPP1 were validated in other independent datasets.
This study provides an integrated view of interactions among DNA methylation and gene expression in patients with KD. MAPK14 and PHLPP1 are the key genes influenced by methylation and may serve as candidate biomarkers for KD.
川崎病（KD）是一种病因不明的儿童热性血管炎。基因表达动力学中的表观遗传调控在 KD 中变得越来越重要。因此，我们进行了 DNA 甲基化和基因表达数据的综合分析，以确定 KD 中的新分子机制和关键功能基因。
从基因表达综合数据库中下载 DNA 甲基化（GSE84624）和基因表达（GSE68004）数据集。将 GSE84624 中差异甲基化基因（DMGs）和 GSE68004 中差异表达基因（DEGs）之间的重叠基因定义为甲基化差异表达基因（mDEGs）。使用 DAVID 数据库对 mDEGs 进行功能富集分析。然后使用 STRING 数据库构建蛋白质-蛋白质相互作用（PPI）网络，以获得参与 KD 的关键基因。
在 KD 与对照样本之间筛选出 1389 个 DMGs 和 1362 个 DEGs。它们的重叠导致 4 个高甲基化/下调和 187 个低甲基化/上调基因。这些 mDEGs 主要富集在炎症反应、先天免疫反应和凝血以及血小板激活、破骨细胞分化和趋化因子信号通路等信号通路中。PPI 网络分析确定 MAPK14 和 PHLPP1 为参与 KD 的关键基因，可将 KD 与其他常见儿科发热性疾病区分开来。此外，在其他独立数据集上验证了 MAPK14 和 PHLPP1 的甲基化和表达水平。
本研究提供了 KD 患者中 DNA 甲基化和基因表达相互作用的综合视图。MAPK14 和 PHLPP1 是受甲基化影响的关键基因，可能成为 KD 的候选生物标志物。
