Jiang Ruiwei, Jones Meaghan J, Sava Francesco, Kobor Michael S, Carlsten Christopher
Centre for Molecular Medicine and Therapeutics, University of British Columbia, 950 west 28th Avenue, Vancouver, V5Z4H4, Canada.
Air Pollution Exposure Laboratory, Chan-Yeung Centre for Occupational and Environmental Lung Disease, Department of Medicine, Division of Respiratory Medicine, University of British Columbia, 2775 Laurel Street, Vancouver, British Columbia, V5Z1L9, Canada.
Part Fibre Toxicol. 2014 Dec 9;11:71. doi: 10.1186/s12989-014-0071-3.
Changes in DNA methylation have been associated with traffic-related air pollution in observational studies, but the specific mechanisms and temporal dynamics therein have not been explored in a controlled study of asthmatics. In this study, we investigate short-term effects of diesel exhaust inhalation on DNA methylation levels at CpG sites across the genome in circulating blood in asthmatics.
A double-blind crossover study of filtered air and diesel exhaust exposures was performed on sixteen non-smoking asthmatic subjects. Blood samples were collected pre-exposure, and then 6 and 30 hours post-exposure. Peripheral blood mononuclear cell DNA methylation was interrogated using the Illumina Infinium HumanMethylation450 Array. Exposure-related changes in DNA methylation were identified. In addition, CpG sites overlapping with Alu or LINE1 repetitive elements and candidate microRNA loci were also analyzed.
DNA methylation at 2827 CpG sites were affected by exposure to diesel exhaust but not filtered air; these sites enriched for genes involved in protein kinase and NFkB pathways. CpG sites with significant changes in response to diesel exhaust exposure primarily became less methylated, with a site residing within GSTP1 being among the significant hits. Diesel exhaust-associated change was also found for CpG sites overlapping with Alu and LINE1 elements as well as for a site within miR-21.
Short-term exposure to diesel exhaust resulted in DNA methylation changes at CpG sites residing in genes involved in inflammation and oxidative stress response, repetitive elements, and microRNA. This provides plausibility for the role of DNA methylation in pathways by which airborne particulate matter impacts gene expression and offers support for including DNA methylation analysis in future efforts to understand the interactions between environmental exposures and biological systems.
在观察性研究中，DNA甲基化变化与交通相关空气污染有关，但在哮喘患者的对照研究中，尚未探究其中的具体机制和时间动态。在本研究中，我们调查了哮喘患者吸入柴油废气对全基因组CpG位点DNA甲基化水平的短期影响。
对16名不吸烟的哮喘患者进行了一项关于过滤空气和柴油废气暴露的双盲交叉研究。在暴露前、暴露后6小时和30小时采集血样。使用Illumina Infinium HumanMethylation450芯片检测外周血单核细胞DNA甲基化情况。确定与暴露相关的DNA甲基化变化。此外，还分析了与Alu或LINE1重复元件以及候选微小RNA基因座重叠的CpG位点。
2827个CpG位点的DNA甲基化受柴油废气暴露影响，但不受过滤空气影响；这些位点富含参与蛋白激酶和NFkB信号通路的基因。对柴油废气暴露有显著变化的CpG位点主要甲基化程度降低，其中GSTP1基因内的一个位点是显著受影响位点之一。在与Alu和LINE1元件重叠的CpG位点以及miR-21内的一个位点也发现了与柴油废气相关的变化。
短期暴露于柴油废气导致参与炎症和氧化应激反应的基因、重复元件以及微小RNA中的CpG位点发生DNA甲基化变化。这为DNA甲基化在空气颗粒物影响基因表达的途径中的作用提供了合理性，并支持在未来理解环境暴露与生物系统相互作用的研究中纳入DNA甲基化分析。
Zotero 插件
