Department of Occupational and Environmental Health Sciences, School of Public Health, Peking University, Beijing, China.
Division of Environmental Health Sciences, School of Public Health and Center for Computational Biology, University of California, Berkeley, Berkeley, CA, USA.
Ecotoxicol Environ Saf. 2022 Jul 1;239:113634. doi: 10.1016/j.ecoenv.2022.113634. Epub 2022 May 24.
Fine particulate matter (PM) is a modifiable environmental risk factor with established adverse effects on human health. However, associations between acute PM fluctuation and DNA methylation remain unknown.
A quasi-experimental study utilizing naturally occurring PM pollution waves (PPWs) was conducted on 32 healthy young adults. Repeated follow-up measurements were performed and participants served as their own controls before, during, and after PPWs. Exposure measurements including indoor and ambient PM levels, and equivalent personal PM exposure were further estimated based on the time-location information. DNA methylation profiles of circulating CD4T cells were obtained using Illumina HumanMethylationEPIC BeadChip. Linear mixed-effect models were applied to estimate the associations between two scenarios (during-PPWs vs. pre-PPWs periods and during-PPWs vs. post-PPWs periods) and methylation level of each CpG site. We further validated their associations with the personal PM exposure, and GO and KEGG analyses and mediation analysis were conducted accordingly.
Data from 26 participants were included in final analysis after quality control. Short-term high PM exposure was associated with DNA methylation changes of participants. Nine differently methylated CpG sites were not only significantly associated with PPWs periods but also with personal PM exposure in 24-h prior to the health examinations (p < 0.01). Gene ontology analysis found that five sites were associated with two pathways relating to membrane protein synthesis. PM-related changes in CpG sites were mediated by sP-selectin, 8-isoPGF2α, EGF, GRO, IL-15, and IFN-α2, with mediated proportions ranging from 9.65% to 23.40%.
This is the first quasi-experimental study showing that short-term high PM exposure could alter the DNA methylation of CD4T cells, which provided valuable information for further exploring underlying biological mechanisms and epigenetic biomarkers for PM-related acute health effects.
细颗粒物（PM）是一种可改变的环境风险因素，其对人类健康有明确的不良影响。然而，急性 PM 波动与 DNA 甲基化之间的关联仍不清楚。
对 32 名健康的年轻成年人进行了一项准实验研究，利用自然发生的 PM 污染波（PPW）。在 PPW 之前、期间和之后，进行了重复的随访测量，参与者自身作为对照。根据时间-地点信息，进一步估计了室内和环境 PM 水平以及等效个人 PM 暴露的暴露测量值。使用 Illumina HumanMethylationEPIC BeadChip 获得循环 CD4T 细胞的 DNA 甲基化谱。应用线性混合效应模型来估计两种情况（PPW 期间与 PPW 之前期间和 PPW 期间与 PPW 之后期间）与每个 CpG 位点的甲基化水平之间的关联。我们进一步验证了它们与个人 PM 暴露的关联，并进行了相应的 GO 和 KEGG 分析和中介分析。
经过质量控制后，共有 26 名参与者的数据纳入最终分析。短期高 PM 暴露与参与者的 DNA 甲基化变化有关。九个不同甲基化的 CpG 位点不仅与 PPW 期间显著相关，而且与健康检查前 24 小时的个人 PM 暴露也显著相关（p<0.01）。GO 分析发现，有五个位点与与膜蛋白合成有关的两条途径相关。PM 相关的 CpG 位点变化由 sP-选择素、8-isoPGF2α、EGF、GRO、IL-15 和 IFN-α2 介导，介导比例在 9.65%至 23.40%之间。
这是第一项准实验研究表明，短期高 PM 暴露可改变 CD4T 细胞的 DNA 甲基化，为进一步探索 PM 相关急性健康影响的潜在生物学机制和表观遗传生物标志物提供了有价值的信息。
