基于甲基化芯片的儿童过敏性紫癜常见中医证型间甲基化差异分析  

Based on methylation chip: Analysis of methylation difference among common TCM Syndromes of Henoch Schonlein purpura in children

作　　者：蔡明阳 苏杭[2] 张博[2] 李盼盼[2] 孙宇莹 吴静静 任献青[2] CAI Ming-yang;SU Hang;ZHANG Bo;LI Pan-pan;SUN Yu-ying;WU Jing-jing;REN Xian-qing(Henan University of Chinese Medicine Zhengzhou Henan 450046,China;First Affiliated Hospital of Henan University of Chinese Medicine,Zhengzhou Henan 450099,China;Beijing University of Chinese Medicine,Beijing 100029,China)

机构地区：[1]河南中医药大学,河南郑州450046 [2]河南中医药大学第一附属医院,河南郑州450099 [3]北京中医药大学,北京100029

出　　处：《时珍国医国药》2021年第7期1759-1762,共4页Lishizhen Medicine and Materia Medica Research

基　　金：国家自然科学基金(U2004107);河南省中医药科学研究专项课题(2019ZYBJ01);河南省特色学科中医学学科建设项目(STS-ZYX-2017010);河南省首批中医药拔尖人才培养项目。

摘　　要：目的应用甲基化芯片技术从DNA甲基化的层面初步阐释过敏性紫癜(Henoch-Sch9nlein Purpura, HSP)风热伤络证与血热妄行证间的DNA甲基化差异,为深入研究HSP证型间差异提供研究基础。方法选取2018年5月至2019年12月,在河南中医药大学第一附属医院儿科门诊就诊的HSP辨证属风热伤络证、血热妄行证的患儿及健康儿童各5例,采用Illumina Human Methylation 850K BeadChip对受试者的全血进行全基因组DNA甲基化检测,筛选差异DNA甲基化位点并对其进行生物学信息分析。结果 HSP风热伤络证、血热妄行证患儿与健康儿之间存在DNA甲基化差异,与正常组相比,两证型分别有754和1397个差异甲基化位点。两证型之间有710个差异甲基化位点,可注释到457个基因。其中NOTCH1、SMAD3、MALT1、SELP、TGFBR2等甲基化差异基因,可能与风热伤络证与血热妄行证之间的差异有关。GO功能和KEGG信号通路富集分析显示,证型间差异基因主要富集在细胞间黏附、细胞间信号转导、Hippo信号通路等功能和通路上。结论 DNA甲基化的差异,可能通过多个生物过程与信号通路,介导HSP中医证型间差异。Objective Using DNA methylation chip technology to preliminarily explain the difference of DNA methylation between the syndrome of wind-heat injuring collaterals and the syndrome of blood-heat of Henoch Schonlein purpura(HSP) from the level of DNA methylation, so as to provide a research basis for further study of the differences between HSP syndromes. Methods Each of 5 children with the syndrome of wind-heat injuring collaterals, the syndrome of blood-heat were selected from the pediatric outpatient department of the First Affiliated Hospital of Henan University of Chinese medicine, and 5 healthy children from May 2018 to December 2019. Beadchip detected the whole-genome DNA methylation of the whole blood of the subjects, screened the different DNA methylation sites, and analyzed their biological information.Results Compared with healthy children, 754 and 1397 differential DNA methylation sites in HSP patients with the syndrome of wind-heat injuring collaterals and the syndrome of blood-heat, respectively. There were 710 differential methylated sites between the two syndromes, which could be annotated to 457 genes. Among them, Notch1, Smad3, MALT1, SELP, TGFBR2, and other methylation differential genes may be related to the difference between the two syndromes. Go and KEGG pathway enrichment analysis showed that the differential genes between syndromes were mainly enriched in intercellular adhesion, intercellular signal transduction, hippo signal pathway, and other functions and pathways. Conclusion The difference of DNA methylation may mediate the difference of TCM syndrome types of HSP through multiple biological processes and signaling pathways.

关 键 词：过敏性紫癜 DNA甲基化 基因芯片 风热伤络证 血热妄行证 

分 类 号：R725.5[医药卫生—儿科]