The association between cumulative exposure to PM2.5 and DNA methylation measured using methyl-capture sequencing among COPD patients

IF 4.7 2区医学 Q1 RESPIRATORY SYSTEM

Respiratory Research Pub Date : 2024-09-09 DOI:10.1186/s12931-024-02955-3

Hyun Woo Ji, Jieun Kang, Hwan-Cheol Kim, Junghee Jung, Seon-Jin Lee, Ji Ye Jung, Sei Won Lee

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Abstract

Particulate matter with a diameter of < 2.5 μm (PM2.5) influences gene regulation via DNA methylation; however, its precise mechanism of action remains unclear. Thus, this study aimed to examine the connection between personal PM2.5 exposure and DNA methylation in CpG islands as well as explore the associated gene pathways. A total of 95 male patients with chronic obstructive pulmonary disease (COPD) were enrolled in this study. PM2.5 concentrations were measured for 12 months, with individual exposure recorded for 24 h every 3 months. Mean indoor and estimated individual PM2.5 exposure levels were calculated for short-term (7 days), mid-term (35 days), and long-term (90 days). DNA methylation analysis was performed on the blood samples, which, after PCR amplification and hybridization, were finally sequenced using an Illumina NovaSeq 6000 system. Correlation between PM2.5 exposure and CpG methylation sites was confirmed via a mixed-effects model. Functional enrichment analysis was performed on unique CpG methylation sites associated with PM2.5 exposure to identify the relevant biological functions or pathways. The number of CpG sites showing differential methylation was 36, 381, and 182 for the short-, mid-, and long-term indoor models, respectively, and 3, 98, and 28 for the short-, mid-, and long-term estimated exposure models, respectively. The representative genes were TMTC2 (p = 1.63 × 10-3, R2 = 0.656), GLRX3 (p = 1.46 × 10-3, R2 = 0.623), DCAF15 (p = 2.43 × 10-4, R2 = 0.623), CNOT6L (p = 1.46 × 10-4, R2 = 0.609), BSN (p = 2.21 × 10-5, R2 = 0.606), and SENP6 (p = 1.59 × 10-4, R2 = 0.604). Functional enrichment analysis demonstrated that the related genes were mostly associated with pathways related to synaptic transmission in neurodegenerative diseases and cancer. A significant association was observed between PM2.5 exposure and DNA methylation upon short-term exposure, and the extent of DNA methylation was the highest upon mid-term exposure. Additionally, various pathways related to neurodegenerative diseases and cancer were associated with patients with COPD. NCT04878367.

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慢性阻塞性肺病患者的 PM2.5 累积暴露量与使用甲基捕获测序法测量的 DNA 甲基化之间的关系

直径小于 2.5 μm 的颗粒物（PM2.5）通过 DNA 甲基化影响基因调控，但其确切的作用机制仍不清楚。因此，本研究旨在研究个人PM2.5暴露与CpG岛DNA甲基化之间的联系，并探索相关的基因通路。本研究共纳入了 95 名男性慢性阻塞性肺病（COPD）患者。PM2.5浓度的测量持续了12个月，每3个月记录一次24小时的个人接触情况。计算了短期（7 天）、中期（35 天）和长期（90 天）的室内平均 PM2.5 暴露水平和估计的个人 PM2.5 暴露水平。对血液样本进行了 DNA 甲基化分析，经过 PCR 扩增和杂交，最后使用 Illumina NovaSeq 6000 系统进行测序。通过混合效应模型确认了 PM2.5 暴露与 CpG 甲基化位点之间的相关性。对与 PM2.5 暴露相关的独特 CpG 甲基化位点进行了功能富集分析，以确定相关的生物功能或通路。在短期、中期和长期室内模型中，出现差异甲基化的 CpG 位点数量分别为 36、381 和 182 个；在短期、中期和长期估计暴露模型中，出现差异甲基化的 CpG 位点数量分别为 3、98 和 28 个。代表性基因为 TMTC2（p = 1.63 × 10-3，R2 = 0.656）、GLRX3（p = 1.46 × 10-3，R2 = 0.623）、DCAF15（p = 2.43 × 10-4，R2 = 0.623）、CNOT6L（p = 1.46 × 10-4，R2 = 0.609）、BSN（p = 2.21 × 10-5，R2 = 0.606）和 SENP6（p = 1.59 × 10-4，R2 = 0.604）。功能富集分析表明，相关基因大多与神经退行性疾病和癌症的突触传递通路有关。短期暴露于PM2.5与DNA甲基化之间存在明显关联，中期暴露时DNA甲基化程度最高。此外，与神经退行性疾病和癌症有关的各种途径都与慢性阻塞性肺病患者有关。NCT04878367。

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来源期刊

Respiratory Research 医学-呼吸系统

自引率

1.70%

发文量

314

期刊介绍： Respiratory Research publishes high-quality clinical and basic research, review and commentary articles on all aspects of respiratory medicine and related diseases. As the leading fully open access journal in the field, Respiratory Research provides an essential resource for pulmonologists, allergists, immunologists and other physicians, researchers, healthcare workers and medical students with worldwide dissemination of articles resulting in high visibility and generating international discussion. Topics of specific interest include asthma, chronic obstructive pulmonary disease, cystic fibrosis, genetics, infectious diseases, interstitial lung diseases, lung development, lung tumors, occupational and environmental factors, pulmonary circulation, pulmonary pharmacology and therapeutics, respiratory immunology, respiratory physiology, and sleep-related respiratory problems.