牙周炎 DNA 甲基化的综合分析。

Comprehensive analysis of DNA methylation for periodontitis.

机构信息

Hebei Key Laboratory of Stomatology, Hebei Clinical Research Center for Oral Diseases, School and Hospital of Stomatology, Hebei Medical University, Shijiazhuang, 050017, People's Republic of China.

出版信息

Int J Implant Dent. 2022 May 2;8(1):22. doi: 10.1186/s40729-022-00420-8.

DOI:10.1186/s40729-022-00420-8

PMID:35491409

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9058047/

Abstract

BACKGROUND

Periodontitis is an infectious disease, and a risk factor for peri-implantitis that could result in the implant loss. DNA methylation has an essential role in the etiology and pathogenesis of inflammatory disease. However, there is lack of study on methylation status of genes in periodontitis. This study sought to explore the gene methylation profiling microarray in periodontitis.

METHODS

Through searching in the Gene Expression Omnibus database, a gene methylation profiling data set GSE173081 was identified, which included 12 periodontitis samples and 12 normal samples, respectively. Thereafter, the data of GSE173081 was downloaded and analyzed to determined differentially methylated genes (DMGs), which then were used to perform Gene Ontology analysis and pathway enrichment analyses through online database. In addition, the DMGs were applied to construct the protein-protein interaction (PPI) network information, predict the hub genes in pathology of periodontitis.

RESULTS

In total 668 DMGs were sorted and identified from the data set, which included 621 hypo-methylated genes and 47 hyper-methylated genes. Through the function and ontology analysis, these 668 genes are mainly classified into intracellular signaling pathway, cell components, cell-cell interaction, and cellular behaviors. The pathway analysis showed that the hypo-methylated genes were mostly enriched in the pathway of cGMP-PKG signaling pathway; RAF/MAP kinase; PI3K-Akt signaling pathway, while hyper-methylated genes were mostly enriched in the pathway of bacterial invasion of epithelial cells; sphingolipid signaling pathway and DCC mediated attractive signaling. The PPI network contained 630 nodes and 1790 interactions. Moreover, further analysis identified top 10 hub genes (APP; PAX6; LPAR1; WNT3A; BMP2; PI3KR2; GATA4; PLCB1; GATA6; CXCL12) as central nodes that are involved in the immune system and the inflammatory response.

CONCLUSIONS

This study provides comprehensive information of methylation status of genes to the revelation of periodontitis pathogenesis that may contribute to future research on periodontitis.

摘要

背景

牙周炎是一种传染病，也是导致种植体周围炎的一个危险因素，可能导致种植体丧失。DNA 甲基化在炎症性疾病的病因和发病机制中起着至关重要的作用。然而，关于牙周炎中基因甲基化状态的研究还很缺乏。本研究旨在探讨牙周炎的基因甲基化谱分析。

方法

通过在基因表达综合数据库中搜索，确定了一个基因甲基化谱数据集 GSE173081，其中包括 12 个牙周炎样本和 12 个正常样本。随后，下载并分析 GSE173081 的数据，以确定差异甲基化基因（DMGs），然后通过在线数据库进行基因本体分析和通路富集分析。此外，还将 DMGs 应用于构建蛋白质-蛋白质相互作用（PPI）网络信息，预测牙周炎发病机制中的关键基因。

结果

从该数据集中共筛选出 668 个 DMGs，其中包括 621 个低甲基化基因和 47 个高甲基化基因。通过功能和本体分析，这些 668 个基因主要分为细胞内信号通路、细胞成分、细胞-细胞相互作用和细胞行为。通路分析表明，低甲基化基因主要富集在 cGMP-PKG 信号通路、RAF/MAP 激酶、PI3K-Akt 信号通路中；而高甲基化基因主要富集在细菌入侵上皮细胞通路、鞘脂信号通路和 DCC 介导的吸引信号通路中。PPI 网络包含 630 个节点和 1790 个相互作用。此外，进一步分析确定了前 10 个关键基因（APP、PAX6、LPAR1、WNT3A、BMP2、PI3KR2、GATA4、PLCB1、GATA6、CXCL12）作为中心节点，参与免疫系统和炎症反应。