Department of Pulmonary and Critical Care Medicine, China-Japan Friendship Hospital, Beijing, China.
Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China.
Front Public Health. 2023 Jan 5;10:1069685. doi: 10.3389/fpubh.2022.1069685. eCollection 2022.
Fine particulate matter (PM) is a crucial risk factor for chronic obstructive pulmonary disease (COPD). However, the mechanisms whereby PM contribute to COPD risk have not been fully elucidated. Accumulating evidence suggests that epigenetics, including DNA methylation, play an important role in this process; however, the association between PM exposure and genome-wide DNA methylation in patients with COPD has not been studied.
To evaluate the association of personal exposure to PM and genome-wide DNA methylation changes in the peripheral blood of patients with COPD.
A panel study was conducted in Beijing, China. We repeatedly measured and collected personal PM data for 72 h. Genome-wide DNA-methylation of peripheral blood was analyzed using the Illumina Infinium Human Methylation BeadChip (850 k). A linear-mixed effect model was used to identify the differentially methylated probe (DMP) associated with PM. Finally, we performed a functional enrichment analysis of the DMPs that were significantly associated with PM.
A total of 24 COPD patients were enrolled and 48 repeated DNA methylation measurements were associated in this study. When the false discovery rate was < 0.05, 19 DMPs were significantly associated with PM and were annotated to corresponding genes. Functional enrichment analysis of these genes showed that they were related to the response to toxic substances, regulation of tumor necrosis factor superfamily cytokine production, regulation of photosensitivity 3-kinase signaling, and other pathways.
This study provided evidence for a significant relationship between personal PM exposure and DNA methylation in patients with COPD. Our research also revealed a new biological pathway explaining the adverse effects of PM exposure on COPD risk.
细颗粒物(PM)是慢性阻塞性肺疾病(COPD)的一个关键危险因素。然而,PM 导致 COPD 风险的机制尚未完全阐明。越来越多的证据表明,表观遗传学,包括 DNA 甲基化,在这一过程中发挥着重要作用;然而,PM 暴露与 COPD 患者全基因组 DNA 甲基化之间的关联尚未得到研究。
评估 PM 暴露与 COPD 患者外周血全基因组 DNA 甲基化变化之间的关联。
在中国北京进行了一项病例对照研究。我们对个人 PM 暴露进行了为期 72 小时的重复测量和收集。使用 Illumina Infinium Human Methylation BeadChip(850 k)分析外周血全基因组 DNA 甲基化。采用线性混合效应模型识别与 PM 相关的差异甲基化探针(DMP)。最后,我们对与 PM 显著相关的 DMP 进行了功能富集分析。
本研究共纳入 24 例 COPD 患者,共进行了 48 次重复 DNA 甲基化测量。当错误发现率<0.05 时,有 19 个 DMP 与 PM 显著相关,并被注释到相应的基因。这些基因的功能富集分析表明,它们与对有毒物质的反应、肿瘤坏死因子超家族细胞因子产生的调节、感光 3-激酶信号的调节等途径有关。
本研究为 PM 暴露与 COPD 患者 DNA 甲基化之间存在显著关系提供了证据。我们的研究还揭示了一个新的生物学途径,解释了 PM 暴露对 COPD 风险的不利影响。