Short-term diesel exhaust inhalation in a controlled human crossover study is associated with changes in DNA methylation of circulating mononuclear cells in asthmatics.
Short-term diesel exhaust inhalation in a controlled human crossover study is associated with changes in DNA methylation of circulating mononuclear cells in asthmatics.
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DOI：
10.1186/s12989-014-0071-3
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发表时间：
2014-12-09
影响因子：
10
通讯作者：
Carlsten C
中科院分区：
文献类型：
--
作者：
Jiang R;Jones MJ;Sava F;Kobor MS;Carlsten C
在观察性研究中，DNA甲基化的变化与交通相关的空气污染有关，但其中的具体机制和时间动力学尚未在哮喘患者的对照研究中探索。在这项研究中，我们调查了吸入柴油废气对哮喘患者循环血液中基因组CpG位点DNA甲基化水平的短期影响。对16名不吸烟的哮喘受试者进行了一项过滤空气和柴油机废气暴露的双盲交叉研究。在暴露前以及暴露后6小时和30小时采集血样。使用Illumina Infinium HumanMethylation 450 Array检测外周血单核细胞DNA甲基化。确定了DNA甲基化的暴露相关变化。此外，还分析了与Alu或LINE 1重复元件重叠的CpG位点和候选microRNA位点。2827个CpG位点的DNA甲基化受到柴油机尾气的影响，但不受过滤空气的影响;这些位点富含蛋白激酶和NF κ B通路相关基因。CpG位点在柴油机尾气暴露后发生显著变化，主要是甲基化程度降低，其中位于GST 1内的位点是显著的命中位点。与Alu和LINE 1元件重叠的CpG位点以及miR-21内的位点也发现了柴油机排气相关的变化。短期暴露于柴油机废气导致CpG位点的DNA甲基化变化，这些位点位于参与炎症和氧化应激反应的基因、重复元件和microRNA中。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可能性，并为在未来的努力中包括DNA甲基化分析以了解环境暴露与生物系统之间的相互作用提供了支持。本文的在线版本（doi：10.1186/s12989-014-0071-3）包含补充材料，可供授权用户使用。
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. The online version of this article (doi:10.1186/s12989-014-0071-3) contains supplementary material, which is available to authorized users.
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影响因子：
3.8
作者：
Dedeurwaerder, Sarah;Defrance, Matthieu;Fuks, Francois
通讯作者：
Fuks, Francois
影响因子：
56.9
作者：
Gaudet, F;Hodgson, JG;Jaenisch, R
通讯作者：
Jaenisch, R
影响因子：
10.4
作者：
Bollati V;Marinelli B;Apostoli P;Bonzini M;Nordio F;Hoxha M;Pegoraro V;Motta V;Tarantini L;Cantone L;Schwartz J;Bertazzi PA;Baccarelli A
通讯作者：
Baccarelli A
影响因子：
5
作者：
Cheng, Yunhui;Liu, Xiaojun;Zhang, Shuo;Lin, Ying;Yang, Jian;Zhang, Chunxiang
通讯作者：
Zhang, Chunxiang
影响因子：
29.4
作者：
de Zoeten EF;Wang L;Sai H;Dillmann WH;Hancock WW
通讯作者：
Hancock WW