Short- and intermediate-term exposure to ambient fine particulate elements and leukocyte epigenome-wide DNA methylation in older men: the Normative Aging Study,Environment International

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Short- and intermediate-term exposure to ambient fine particulate elements and leukocyte epigenome-wide DNA methylation in older men: the Normative Aging Study
Environment International ( IF 11.8 ) Pub Date : 2021-10-28 , DOI: 10.1016/j.envint.2021.106955
Cuicui Wang ₁ , Andres Cardenas ₂ , John N Hutchinson ₃ , Allan Just ₄ , Jonathan Heiss ₄ , Lifang Hou ₅ , Yinan Zheng ₅ , Brent A Coull ₃ , Anna Kosheleva ₁ , Petros Koutrakis ₁ , Andrea A Baccarelli ₆ , Joel D Schwartz ₇

Affiliation

Background

Several epigenome-wide association studies (EWAS) of ambient particulate matter with aerodynamic diameter ≤ 2.5 µm (PM_2.5) have been reported. However, EWAS of PM_2.5 elements (PEs), reflecting different emission sources, are very limited.

Objectives

We performed EWAS of short- and intermediate-term exposure to PM_2.5 and 13 PEs. We hypothesized that significant changes in DNAm may vary by PM_2.5 mass and its elements.

Methods

We repeatedly collected blood samples in the Normative Aging Study and measured leukocyte DNA methylation (DNAm) with the Illumina HumanMethylation450K BeadChip. We collected daily PM_2.5 and 13 PEs at a fixed central site. To estimate the associations between each PE and DNAm at individual cytosine-phosphate-guanine (CpG) sites, we incorporated a distributed-lag (0–27 d) term in the setting of median regression with subject-specific intercept and examined cumulative lag associations. We also accounted for selection bias due to loss to follow-up and mortality prior to enrollment. Significantly differentially methylated probes (DMPs) were identified using Bonferroni correction for multiple testing. We further conducted regional and pathway analyses to identify significantly differentially methylated regions (DMRs) and pathways.

Results

We included 695 men with 1,266 visits between 1999 and 2013. The subjects had a mean age of 75 years. The significant DMPs, DMRs, and pathways varied by to PM_2.5 total mass and PEs. For example, PM_2.5 total mass was associated with 2,717 DMPs and 10,470 DMRs whereas Pb was associated with 3,173 DMPs and 637 DMRs. The identified pathways by PM_2.5 mass were mostly involved in mood disorders, neuroplasticity, immunity, and inflammation, whereas the pathways associated with motor vehicles (BC, Cu, Pb, and Zn) were related with cardiovascular disease and cancer (e.g., “PPARs signaling”).

Conclusions

PM_2.5 and PE were associated with methylation changes at multiple probes and along multiple pathways, in ways that varied by particle components.

中文翻译：

老年男性中短期和中期暴露于环境细颗粒元素和白细胞表观基因组范围的 DNA 甲基化：规范老化研究

背景

已经报道了空气动力学直径 ≤ 2.5 µm (PM _2.5 )的环境颗粒物的几项表观基因组范围关联研究 (EWAS) 。然而，反映不同排放源的 PM _2.5元素 (PE) 的EWAS非常有限。

目标

我们对 PM _2.5和 13 PE的短期和中期暴露进行了 EWAS 。我们假设 DNAm 的显着变化可能因 PM _2.5质量及其元素而异。

方法

我们在规范老化研究中反复收集血液样本，并使用 Illumina HumanMethylation450K BeadChip 测量白细胞 DNA 甲基化 (DNAm)。我们每天收集 PM _2.5固定中心站点的 13 个 PE。为了估计单个胞嘧啶 - 磷酸 - 鸟嘌呤（CpG）位点的每个 PE 和 DNAm 之间的关联，我们在中位数回归的设置中加入了一个分布式滞后（0-27 天）项，并检查了累积滞后关联. 我们还考虑了由于失访和入组前死亡率导致的选择偏倚。使用 Bonferroni 校正进行多重测试鉴定显着差异甲基化探针 (DMP)。我们进一步进行了区域和通路分析，以确定显着差异甲基化区域 (DMR) 和通路。

结果

我们纳入了 695 名男性，在 1999 年至 2013 年间访问了 1,266 次。受试者的平均年龄为 75 岁。显着的 DMP、DMR 和途径因 PM _2.5总质量和 PE而异。例如，PM _2.5总质量与 2,717 个 DMP 和 10,470 个 DMR 相关，而 Pb 与 3,173 个 DMP 和 637 个 DMR 相关。PM _2.5质量确定的通路主要涉及情绪障碍、神经可塑性、免疫和炎症，而与机动车辆相关的通路（BC、Cu、Pb 和 Zn）与心血管疾病和癌症相关（例如，“PPARs信号”）。