Air pollution and gene-specific methylation in the Normative Aging Study
Air pollution and gene-specific methylation in the Normative Aging Study
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DOI：
10.4161/epi.27584
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发表时间：
2014-03-01
期刊：
影响因子：
3.7
通讯作者：
Schwartz, Joel
中科院分区：
文献类型：
--
作者：
Bind, Marie-Abele;Lepeule, Johanna;Schwartz, Joel
空气污染对人体产生多系统影响的机制尚未完全阐明，但似乎包括炎症和血栓形成。这项研究考察了臭氧浓度和细颗粒物的组成是否与组织因子(F3)、干扰素-γ(干扰素-γ)、白介素6(IL-6)、Toll样受体2(TLR-2)和细胞间黏附分子-1(ICAM-1)的甲基化变化有关。我们调查了参加标准化老龄化研究(1999-2009)的777名老年男性，空气污染暴露与基因特异性甲基化之间的关系。我们反复测量每个基因启动子区域内多个CpG位点的甲基化，并计算特定位置测量的平均值。我们用分布滞后模型检验了初级和次级空气污染物之间的中期关联，以及每个部位的平均甲基化和甲基化。空气污染物浓度的增加与F3、ICAM-1和TLR-2低甲基化以及干扰素和IL-6高甲基化显著相关。在评估之前的四周内，黑碳浓度平均四分位数范围内的增加与F3甲基化减少12%相关(95%可信区间：-17%至-6%)。对于一些基因，甲基化的变化只在启动子区域的特定位置观察到。DNA甲基化可能反映了空气污染的生物影响。我们发现，炭黑通过减少F3甲基化而对纤维蛋白原产生显著的调节作用，硫酸盐和臭氧通过减少ICAM-1甲基化而对ICAM-1蛋白产生显著的调节作用。
The mechanisms by which air pollution has multiple systemic effects in humans are not fully elucidated, but appear to include inflammation and thrombosis. This study examines whether concentrations of ozone and components of fine particle mass are associated with changes in methylation on tissue factor (F3), interferon gamma (IFN-), interleukin 6 (IL-6), toll-like receptor 2 (TLR-2), and intercellular adhesion molecule 1 (ICAM-1). We investigated associations between air pollution exposure and gene-specific methylation in 777 elderly men participating in the Normative Aging Study (1999-2009). We repeatedly measured methylation at multiple CpG sites within each gene's promoter region and calculated the mean of the position-specific measurements. We examined intermediate-term associations between primary and secondary air pollutants and mean methylation and methylation at each position with distributed-lag models. Increase in air pollutants concentrations was significantly associated with F3, ICAM-1, and TLR-2 hypomethylation, and IFN- and IL-6 hypermethylation. An interquartile range increase in black carbon concentration averaged over the four weeks prior to assessment was associated with a 12% reduction in F3 methylation (95% CI: -17% to -6%). For some genes, the change in methylation was observed only at specific locations within the promoter region. DNA methylation may reflect biological impact of air pollution. We found some significant mediated effects of black carbon on fibrinogen through a decrease in F3 methylation, and of sulfate and ozone on ICAM-1 protein through a decrease in ICAM-1 methylation.