Department of Environmental Health; Harvard School of Public Health; Boston, MA USA; Department of Biostatistics; Harvard School of Public Health; Boston, MA USA.
Department of Environmental Health; Harvard School of Public Health; Boston, MA USA.
Epigenetics. 2014 Mar;9(3):448-58. doi: 10.4161/epi.27584. Epub 2014 Jan 2.
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-γ), 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-γ 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.
空气污染对人体产生多种系统性影响的机制尚未完全阐明，但似乎包括炎症和血栓形成。本研究探讨了臭氧和细颗粒物质量成分浓度是否与组织因子 (F3)、干扰素 γ (IFN-γ)、白细胞介素 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 777 名参与正常老化研究（1999-2009 年）的老年男性的空气污染暴露与基因特异性甲基化之间的关联。我们在每个基因的启动子区域内重复测量了多个 CpG 位点的甲基化，并计算了位置特异性测量的平均值。我们用分布式滞后模型检验了主要和次要空气污染物与平均甲基化和每个位置甲基化之间的中期关联。空气污染物浓度的增加与 F3、ICAM-1 和 TLR-2 低甲基化以及 IFN-γ 和 IL-6 高甲基化显著相关。在评估前四周内平均黑碳浓度的四分位间距增加与 F3 甲基化减少 12%（95%CI：-17%至-6%）相关。对于某些基因，甲基化的变化仅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学影响。我们发现，通过 F3 甲基化减少，黑碳对纤维蛋白原具有一些显著的介导作用，通过 ICAM-1 甲基化减少，硫酸盐和臭氧对 ICAM-1 蛋白具有一些显著的介导作用。
