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交通衍生颗粒物暴露与组蛋白H3修饰:一项重复测量研究。

Traffic-derived particulate matter exposure and histone H3 modification: A repeated measures study.

作者信息

Zheng Yinan, Sanchez-Guerra Marco, Zhang Zhou, Joyce Brian T, Zhong Jia, Kresovich Jacob K, Liu Lei, Zhang Wei, Gao Tao, Chang Dou, Osorio-Yanez Citlalli, Carmona Juan Jose, Wang Sheng, McCracken John P, Zhang Xiao, Chervona Yana, Díaz Anaite, Bertazzi Pier A, Koutrakis Petros, Kang Choong-Min, Schwartz Joel, Baccarelli Andrea A, Hou Lifang

机构信息

Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA; Health Sciences Integrated PhD Program, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.

Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, MA, USA; Department of Developmental Neurobiology, National Institute of Perinatology, Mexico City, Mexico.

出版信息

Environ Res. 2017 Feb;153:112-119. doi: 10.1016/j.envres.2016.11.015. Epub 2016 Dec 3.

Abstract

BACKGROUND

Airborne particulate matter (PM) may induce epigenetic changes that potentially lead to chronic diseases. Histone modifications regulate gene expression by influencing chromatin structure that can change gene expression status. We evaluated whether traffic-derived PM exposure is associated with four types of environmentally inducible global histone H3 modifications.

METHODS

The Beijing Truck Driver Air Pollution Study included 60 truck drivers and 60 office workers examined twice, 1-2 weeks apart, for ambient PM (both day-of and 14-day average exposures), personal PM, black carbon (BC), and elemental components (potassium, sulfur, iron, silicon, aluminum, zinc, calcium, and titanium). For both PM measures, we obtained hourly ambient PM data for the study period from the Beijing Municipal Environmental Bureau's 27 representatively distributed monitoring stations. We then calculated a 24h average for each examination day and a moving average of ambient PM measured in the 14 days prior to each examination. Examinations measured global levels of H3 lysine 9 acetylation (H3K9ac), H3 lysine 9 tri-methylation (H3K9me3), H3 lysine 27 tri-methylation (H3K27me3), and H3 lysine 36 tri-methylation (H3K36me3) in blood leukocytes collected after work. We used adjusted linear mixed-effect models to examine percent changes in histone modifications per each μg/m increase in PM exposure.

RESULTS

In all participants each μg/m increase in 14-day average ambient PM exposure was associated with lower H3K27me3 (β=-1.1%, 95% CI: -1.6, -0.6) and H3K36me3 levels (β=-0.8%, 95% CI: -1.4, -0.1). Occupation-stratified analyses showed associations between BC and both H3K9ac and H3K36me3 that were stronger in office workers (β=4.6%, 95% CI: 0.9, 8.4; and β=4.1%, 95% CI: 1.3; 7.0 respectively) than in truck drivers (β=0.1%, 95% CI: -1.3, 1.5; and β=0.9%, 95% CI: -0.9, 2.7, respectively; both p <0.05). Sex-stratified analyses showed associations between examination-day PM and H3K9ac, and between BC and H3K9me3, were stronger in women (β=10.7%, 95% CI: 5.4, 16.2; and β=7.5%, 95% CI: 1.2, 14.2, respectively) than in men (β=1.4%, 95% CI: -0.9, 3.7; and β=0.9%, 95% CI: -0.9, 2.7, respectively; both p <0.05). We observed no associations between personal PM or elemental components and histone modifications.

CONCLUSIONS

Our results suggest a possible role of global histone H3 modifications in effects of traffic-derived PM exposures, particularly BC exposure. Future studies should assess the roles of these modifications in human diseases and as potential mediators of air pollution-induced disease, in particular BC exposure.

摘要

背景

空气中的颗粒物(PM)可能会引起表观遗传变化,进而可能导致慢性疾病。组蛋白修饰通过影响染色质结构来调节基因表达,而染色质结构的改变会改变基因表达状态。我们评估了交通源PM暴露是否与四种环境诱导的全基因组组蛋白H3修饰有关。

方法

“北京卡车司机空气污染研究”纳入了60名卡车司机和60名办公室职员,对他们进行两次检查,每次间隔1 - 2周,检测环境PM(当日和14天平均暴露量)、个人PM、黑碳(BC)以及元素成分(钾、硫、铁、硅、铝、锌、钙和钛)。对于两种PM测量指标,我们从北京市环境局分布在27个具有代表性地点的监测站获取了研究期间每小时的环境PM数据。然后我们计算了每个检查日的24小时平均值以及每次检查前14天测量的环境PM的移动平均值。检查测量了工作后采集的血液白细胞中H3赖氨酸9乙酰化(H3K9ac)、H3赖氨酸9三甲基化(H3K9me3)、H3赖氨酸27三甲基化(H3K27me3)和H3赖氨酸36三甲基化(H3K36me3)的总体水平。我们使用调整后的线性混合效应模型来检验PM暴露每增加1μg/m³时组蛋白修饰的百分比变化。

结果

在所有参与者中,14天平均环境PM暴露每增加1μg/m³与较低的H3K27me3水平(β = -1.1%,95%置信区间:-1.6,-0.6)和H3K36me3水平(β = -0.8%,95%置信区间:-1.4,-0.1)相关。职业分层分析显示,BC与H3K9ac和H3K36me3之间的关联在办公室职员中更强(β = 4.6%,95%置信区间:0.9,8.4;以及β = 4.1%,95%置信区间:1.3,7.0),而在卡车司机中较弱(β = 0.1%,95%置信区间:-1.3,1.5;以及β = 0.9%,95%置信区间:-0.9,2.7;p均<0.05)。性别分层分析显示,检查日PM与H3K9ac之间以及BC与H3K9me3之间的关联在女性中更强(β = 10.7%,95%置信区间:5.4,16.2;以及β = 7.5%,95%置信区间:1.2,14.2),而在男性中较弱(β = 1.4%,95%置信区间:-0.9,3.7;以及β = 0.9%,95%置信区间:-0.9,2.7;p均<0.05)。我们未观察到个人PM或元素成分与组蛋白修饰之间存在关联。

结论

我们的结果表明全基因组组蛋白H3修饰在交通源PM暴露,特别是BC暴露的影响中可能发挥作用。未来的研究应评估这些修饰在人类疾病中的作用以及作为空气污染所致疾病潜在介质的作用,尤其是BC暴露。

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