目的:本研究的目的是系统回顾评估DNA甲基化变异与食物过敏(FA)相关研究的证据。
方法:在多个数据库中对文献和荟萃分析进行了系统综述。然而,未评估纳入文章中的偏倚风险.
方法:PubMed,Cochrane系统评价数据库,和WebofScience被用来搜索到2022年7月。
方法:我们纳入了靶向和全表观基因组关联研究(EWAS),评估了成人或儿科人群中与FA相关的DNA甲基化改变。
结果:在366种出版物中,只保留了16个,主要集中在儿童的FA。七项候选基因靶向研究发现了Th1/Th2失衡的关联(IL4,IL5,IL10,INFG,IL2和IL12B基因),调节性T细胞功能(FOXP3基因),Toll样受体通路(TLR2、CD14基因)和消化屏障完整性(FLG基因)。9个EWAS评估了与花生过敏的关联(n=3),牛奶过敏(n=2)或各种食物过敏原(n=4)。他们在至少两项研究中强调了11个差异甲基化位点(RPS6KA2,CAMTA1,CTBP2,RYR2,TRAPPC9,DOCK1,GALNTL4,HDAC4,UMODL1,ZAK和TNS3基因)。其中,CAMTA1和RPS6KA2和CTBP2参与调节性T细胞功能和Th2细胞分化,分别。基因功能分析揭示了参与免疫应答和蛋白质磷酸化的两个富集的基因簇。ChIP-X富集分析3显示八个显著的转录因子(RXRA,ZBTB7A,ESR1,TCF3,MYOD1,CTCF,GATA3和CBX2)。独创性路径分析确定了所涉及的典型路径分析,其中,在B细胞发育中,病原体诱导的细胞因子风暴信号通路和树突状细胞成熟。
结论:这篇综述强调了Th1/Th2基因座的表观基因组改变和调节性T细胞分化在候选基因研究和EWAS中的参与。这些改变提供了对FA发病机理的机制方面的更好的了解,并可能指导基于表观基因组的FA生物标志物的开发。
The aim of this study was to systematically
review the evidence across studies that assessed DNA methylome variations in association with food allergy (FA).
A systematic
review of the literature and meta-analysis were carried out within several databases. However, the risk of bias in the included articles was not evaluated.
PubMed, Cochrane Database of Systematic Reviews, and Web of Science were used to search up to July 2022.
We included targeted and epigenome-wide association studies (EWASs) that assessed DNA methylome alterations in association with FA in adult or paediatric populations.
Among 366 publications, only 16 were retained, which were mainly focused on FA in children. Seven candidate gene-targeted studies found associations in Th1/Th2 imbalance (IL4, IL5, IL10, INFG, IL2 and IL12B genes), regulatory T cell function (FOXP3 gene), Toll-like receptors pathway (TLR2, CD14 genes) and digestive barrier integrity (FLG gene). Nine EWAS assessed the association with peanut allergy (n = 3), cow\'s milk allergy (n = 2) or various food allergens (n = 4). They highlighted 11 differentially methylated loci in at least two studies (RPS6KA2, CAMTA1, CTBP2, RYR2, TRAPPC9, DOCK1, GALNTL4, HDAC4, UMODL1, ZAK and TNS3 genes). Among them, CAMTA1 and RPS6KA2, and CTBP2 are involved in regulatory T cell function and Th2 cell differentiation, respectively. Gene-functional analysis revealed two enriched gene clusters involved in immune responses and protein phosphorylation. ChIP-X Enrichment Analysis 3 showed eight significant transcription factors (RXRA, ZBTB7A, ESR1, TCF3, MYOD1, CTCF, GATA3 and CBX2). Ingenuity Pathway Analysis identified canonical pathways involved, among other, in B cell development, pathogen-induced cytokine storm signalling pathway and dendritic cell maturation.
This
review highlights the involvement of epigenomic alterations of loci in Th1/Th2 and regulatory T cell differentiation in both candidate gene studies and EWAS. These alterations provide a better insight into the mechanistic aspects in FA pathogenesis and may guide the development of epigenome-based biomarkers for FA.