Department of Pulmonary and Critical Care Medicine, Peking University Third Hospital, No.49, Huayuan North Road, Haidian District, Beijing, 100191, China.
Department of Pulmonary and Critical Care Medicine, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, China.
Clin Epigenetics. 2024 Oct 8;16(1):139. doi: 10.1186/s13148-024-01750-7.
DNA methylation plays a critical role in asthma development, but differences in DNA methylation among adults with varying asthma severity are less well-defined.
To examine how DNA methylomic patterns differ among adults with asthma based on asthma severity and airway inflammation.
Peripheral blood T cells from 35 adults with asthma in Beijing, China, were serially collected over time (130 samples total) and analyzed for global DNA methylation using the Illumina MethylationEPIC Array. Differential methylation was compared among subjects with varying airway inflammation and severity, as measured by fraction of exhaled nitric oxide, forced expiratory volume in one second (FEV1), and Asthma Control Test (ACT) scores.
Significant differences in DNA methylation were noted among subjects with different degrees of airway inflammation and asthma severity. These differences in DNA methylation were annotated to genes that were enriched in pathways related to asthma or T cell function and included gene ontology categories related to MHC class II assembly, T cell activation, interleukin (IL)-1, and IL-12. Genes related to P450 drug metabolism, glutathione metabolism, and developmental pathways were also differentially methylated in comparisons between subjects with high vs low FEV1 and ACT. Notable genes that were differentially methylated based on asthma severity included RUNX3, several members of the HLA family, AGT, PTPRC, PTPRJ, and several genes downstream of the JAK2 and TNF signaling pathway.
These findings demonstrate how adults with asthma of varying severity possess differences in peripheral blood T cell DNA methylation that contribute to differences in clinical indices of asthma.
DNA 甲基化在哮喘发病机制中起着关键作用，但不同严重程度的哮喘患者之间的 DNA 甲基化差异尚未得到充分定义。
研究基于哮喘严重程度和气道炎症，哮喘患者的 DNA 甲基化图谱如何存在差异。
从中国北京的 35 名哮喘成人中连续采集外周血 T 细胞（共采集 130 个样本），并使用 Illumina MethylationEPIC 阵列进行全基因组 DNA 甲基化分析。通过呼出气一氧化氮（FeNO）分数、用力呼气量（FEV1）和哮喘控制测试（ACT）评分，比较气道炎症和严重程度不同的患者之间的差异甲基化。
不同气道炎症和哮喘严重程度的患者之间存在明显的 DNA 甲基化差异。这些 DNA 甲基化差异与哮喘或 T 细胞功能相关的途径中基因注释相关，包括与 MHC Ⅱ类组装、T 细胞激活、白细胞介素（IL）-1 和 IL-12 相关的基因本体类别。在比较 FEV1 和 ACT 高与低的患者时，与 P450 药物代谢、谷胱甘肽代谢和发育途径相关的基因也存在差异甲基化。基于哮喘严重程度差异甲基化的显著基因包括 RUNX3、HLA 家族的几个成员、AGT、PTPRC、PTPRJ 和 JAK2 和 TNF 信号通路下游的几个基因。
这些发现表明，不同严重程度的哮喘成人在外周血 T 细胞 DNA 甲基化方面存在差异，这些差异导致哮喘的临床指标存在差异。
