哮喘患者外周血全基因组DNA甲基化检测及临床意义分析  

Detection and clinical significance of DNA methylation in peripheral blood of asthmatic patients

作　　者：张露露[1] 王炯[1] Zhang Lulu;Wang Jiong(Dept of Geriatric Respiratory and Critical Care Medicine,The First Affiliated Hospital of Anhui Medical University,Hefei 230022)

机构地区：[1]安徽医科大学第一附属医院老年呼吸与危重症医学科,合肥230022

出　　处：《安徽医科大学学报》2020年第8期1275-1279,共5页Acta Universitatis Medicinalis Anhui

基　　金：安徽省自然科学基金(编号:1608085MH191)。

摘　　要：目的探讨哮喘患者和健康对照者外周血基因组DNA甲基化差异及其临床意义。方法收集诊断明确的哮喘急性发作期成人患者及健康对照者2 ml外周血标本,提取外周血DNA之后,采用Illumina DNA甲基化芯片检测全基因组DNA甲基化水平,并与下载GSE56553数据库中96个基因芯片数据样本取交集,对差异基因功能通路进行生物学分析。结果哮喘患者与健康对照者外周血基因组DNA甲基化程度差异有统计学意义,发现差异基因1493个,其中甲基化程度上调基因有923个,甲基化程度降低基因有570个,GO和KEGG通路功能富集分析获得的差异基因主要集中于参与突触信号传导调控,肌肉收缩,细胞黏附等生物过程,通过构建基因相互作用网络筛选出了TNF、GNB1、PIK3R1、CDC5L、IL-10、CD44等24个关键基因。结论哮喘患者外周血与健康对照者比较,基因组DNA甲基化程度差异有统计学意义,这种差异很有可能是哮喘发生发展的原因。利用生物信息学方法筛选出哮喘发生发展过程中的关键基因和信号通路,可以为哮喘治疗提供新靶点和策略。Objective To investigate the differences of genomic DNA methylation in peripheral blood between asthmatic patients and healthy controls and its clinical significance.Methods 2 ml peripheral blood were collected from patients with acute exacerbation of asthma and healthy controls.After extracting peripheral blood DNA,the whole genome DNA methylation was detected by Illumina DNA methylation gene chip,and they were intersected with the 96 gene chip data samples in the download GSE56553 data set,then they were performed biological analysis on the functional pathways of different genes.Results There was a statistically significant difference in peripheral blood genomic DNA methylation between patients with asthma and healthy people.1493 differential genes were found,of which 923 were methylation-up-regulated genes and 570 were methylation-reduced genes.The differential genes obtained by functional enrichment analysis of GO and KEGG pathways were mainly involved in the processes of the regulation of synaptic signaling,muscle contraction,and cell adhesion.By constructing the gene interaction network,TNF,GNB1,PIK3 R1,CDC5 L,IL-10,CD44 and other 24 key genes were screened.Conclusion Differences in genomic DNA methylation between peripheral blood and healthy controls are statistically significant,and these differences may be the main causes of initiation and progression of asthma.The use of bioinformatics methods to screen out the key genes and signaling pathways in the development of asthma can provide new targets and strategies for asthma treatment.

关 键 词：哮喘 DNA甲基化 基因芯片 GO/KEGG功能富集分析 

分 类 号：R562.2[医药卫生—呼吸系统]