School of Public Health, Key Lab of Public Health Safety of the Ministry of Education and Key Lab of Health Technology Assessment of the Ministry of Health, Fudan University, Shanghai, China.
Biostatistics and Computational Biology Branch, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina.
Am J Epidemiol. 2018 Mar 1;187(3):484-493. doi: 10.1093/aje/kwx277.
Air pollution may increase cardiovascular and respiratory risk through inflammatory pathways, but evidence for acute effects has been weak and indirect. Between December 2014 and July 2015, we enrolled 36 healthy, nonsmoking college students for a panel study in Shanghai, China, a city with highly variable levels of air pollution. We measured personal exposure to particulate matter with an aerodynamic diameter less than or equal to 2.5 μm (PM2.5) continuously for 72 hours preceding each of 4 clinical visits that included phlebotomy. We measured 4 inflammation proteins and DNA methylation at nearby regulatory cytosine-phosphate-guanine (CpG) loci. We applied linear mixed-effect models to examine associations over various lag times. When results suggested mediation, we evaluated methylation as mediator. Increased PM2.5 concentration was positively associated with all 4 inflammation proteins and negatively associated with DNA methylation at regulatory loci for tumor necrosis factor alpha (TNF-α) and soluble intercellular adhesion molecule-1. A 10-μg/m3 increase in average PM2.5 during the 24 hours preceding blood draw corresponded to a 4.4% increase in TNF-α and a statistically significant decrease in methylation at one of the two studied candidate CpG loci for TNF-α. Epigenetics may play an important role in mediating effects of PM2.5 on inflammatory pathways.
空气污染可能通过炎症途径增加心血管和呼吸道风险，但急性效应的证据一直较弱且间接。2014 年 12 月至 2015 年 7 月，我们在中国上海的一项队列研究中招募了 36 名健康、不吸烟的大学生，上海是一个空气污染水平高度变化的城市。我们在 4 次临床就诊前连续 72 小时连续测量个人细颗粒物（PM2.5）暴露情况，这 4 次就诊都包括采血。我们测量了 4 种炎症蛋白和附近调控胞嘧啶-磷酸-鸟嘌呤（CpG）位点的 DNA 甲基化。我们应用线性混合效应模型在不同的滞后时间内检验关联。当结果提示存在中介作用时，我们将甲基化作为中介进行评估。PM2.5 浓度的增加与所有 4 种炎症蛋白呈正相关，与肿瘤坏死因子-α（TNF-α）和可溶性细胞间黏附分子-1 的调控位点的 DNA 甲基化呈负相关。在采血前 24 小时内平均 PM2.5 增加 10μg/m3，对应于 TNF-α 增加 4.4%，且 TNF-α 的两个候选 CpG 位点之一的甲基化水平显著下降。表观遗传学可能在介导 PM2.5 对炎症途径的影响方面发挥重要作用。
