Berlin Institute of Health at Charité - Universitätsmedizin Berlin, Center of Digital Health, Molecular Epidemiology Unit, Charitéplatz 1, 10117, Berlin, Germany; Freie Universität Berlin, Institute for Biology, Königin-Luise-Strasse 12-16, 14195, Berlin, Germany.
Fraunhofer Institute for Biomedical Engineering IBMT, Josef-von-Fraunhofer-Weg 1, 66280, Sulzbach, Germany.
Environ Res. 2023 Sep 15;233:116413. doi: 10.1016/j.envres.2023.116413. Epub 2023 Jun 20.
While the link between exposure to high levels of ambient particulate matter (PM) and increased incidences of respiratory and cardiovascular diseases is widely recognized, recent epidemiological studies have shown that low PM concentrations are equally associated with adverse health effects. As DNA methylation is one of the main mechanisms by which cells regulate and stabilize gene expression, changes in the methylome could constitute early indicators of dysregulated signaling pathways. So far, little is known about PM-associated DNA methylation changes in the upper airways, the first point of contact between airborne pollutants and the human body. Here, we focused on cells of the upper respiratory tract and assessed their genome-wide DNA methylation pattern to explore exposure-associated early regulatory changes. Using a mobile epidemiological laboratory, nasal lavage samples were collected from a cohort of 60 adults that lived in districts with records of low (Simmerath) or moderate (Stuttgart) PM levels in Germany. PM concentrations were verified by particle measurements on the days of the sample collection and genome-wide DNA methylation was determined by enzymatic methyl sequencing at single-base resolution. We identified 231 differentially methylated regions (DMRs) between moderately and lowly PM exposed individuals. A high proportion of DMRs overlapped with regulatory elements, and DMR target genes were involved in pathways regulating cellular redox homeostasis and immune response. In addition, we found distinct changes in DNA methylation of the HOXA gene cluster whose methylation levels have previously been linked to air pollution exposure but also to carcinogenesis in several instances. The findings of this study suggest that regulatory changes in upper airway cells occur at PM levels below current European thresholds, some of which may be involved in the development of air pollution-related diseases.
虽然暴露于高水平的环境颗粒物（PM）与呼吸道和心血管疾病发病率增加之间的联系已被广泛认可，但最近的流行病学研究表明，低 PM 浓度同样与不良健康影响有关。由于 DNA 甲基化是细胞调节和稳定基因表达的主要机制之一，甲基组的变化可能构成失调信号通路的早期指标。到目前为止，人们对空气中污染物与人体首次接触的上呼吸道中与 PM 相关的 DNA 甲基化变化知之甚少。在这里，我们专注于上呼吸道细胞，并评估了它们的全基因组 DNA 甲基化模式，以探索与暴露相关的早期调节变化。使用移动流行病学实验室，从居住在德国 PM 水平记录为低（Simmerath）或中等（Stuttgart）的地区的 60 名成年人队列中收集鼻冲洗样本。在样本采集当天通过颗粒测量验证 PM 浓度，并通过酶促甲基测序以单碱基分辨率确定全基因组 DNA 甲基化。我们确定了中度和低度 PM 暴露个体之间的 231 个差异甲基化区域（DMR）。DMR 中有很大一部分与调节元件重叠，DMR 靶基因参与调节细胞氧化还原稳态和免疫反应的途径。此外，我们发现 HOXA 基因簇的 DNA 甲基化水平发生了明显变化，该基因簇的甲基化水平先前与空气污染暴露有关，但在某些情况下也与致癌作用有关。这项研究的结果表明，在上呼吸道细胞中发生的调节变化发生在低于当前欧洲阈值的 PM 水平，其中一些可能与与空气污染相关的疾病的发展有关。
