COPD 患者中使用甲基化捕获测序测量的 PM 累积暴露与 DNA 甲基化之间的关联。

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

机构信息

Division of Pulmonology, Department of Internal Medicine, National Health Insurance Service Ilsan Hospital, Goyang, Republic of Korea.

Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Ilsan Paik Hospital, Inje University College of Medicine, Goyang, Republic of Korea.

出版信息

Respir Res. 2024 Sep 9;25(1):335. doi: 10.1186/s12931-024-02955-3.

DOI:10.1186/s12931-024-02955-3

PMID:39251997

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11386081/

Abstract

BACKGROUND

Particulate matter with a diameter of < 2.5 μm (PM) influences gene regulation via DNA methylation; however, its precise mechanism of action remains unclear. Thus, this study aimed to examine the connection between personal PM exposure and DNA methylation in CpG islands as well as explore the associated gene pathways.

METHODS

A total of 95 male patients with chronic obstructive pulmonary disease (COPD) were enrolled in this study. PM concentrations were measured for 12 months, with individual exposure recorded for 24 h every 3 months. Mean indoor and estimated individual PM 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 PM exposure and CpG methylation sites was confirmed via a mixed-effects model. Functional enrichment analysis was performed on unique CpG methylation sites associated with PM exposure to identify the relevant biological functions or pathways.

RESULTS

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, R = 0.656), GLRX3 (p = 1.46 × 10, R = 0.623), DCAF15 (p = 2.43 × 10, R = 0.623), CNOT6L (p = 1.46 × 10, R = 0.609), BSN (p = 2.21 × 10, R = 0.606), and SENP6 (p = 1.59 × 10, R = 0.604). Functional enrichment analysis demonstrated that the related genes were mostly associated with pathways related to synaptic transmission in neurodegenerative diseases and cancer.

CONCLUSION

A significant association was observed between PM 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.

GOV IDENTIFIER

NCT04878367.

摘要

背景

直径小于 2.5μm 的颗粒物（PM）通过 DNA 甲基化影响基因调控；然而，其确切的作用机制尚不清楚。因此，本研究旨在探讨个体 PM 暴露与 CpG 岛 DNA 甲基化之间的联系，并探索相关的基因途径。

方法

本研究共纳入 95 例男性慢性阻塞性肺疾病（COPD）患者。对 PM 浓度进行了 12 个月的监测，每 3 个月记录一次 24 小时的个体暴露情况。计算了短期（7 天）、中期（35 天）和长期（90 天）的室内平均和个体估计 PM 暴露水平。对血液样本进行 DNA 甲基化分析，经 PCR 扩增和杂交后，最终使用 Illumina NovaSeq 6000 系统进行测序。通过混合效应模型证实 PM 暴露与 CpG 甲基化位点之间的相关性。对与 PM 暴露相关的独特 CpG 甲基化位点进行功能富集分析，以确定相关的生物学功能或途径。

结果

短期、中期和长期室内模型中，CpG 位点差异甲基化的数量分别为 36、381 和 182 个，短期、中期和长期个体估计暴露模型中分别为 3、98 和 28 个。代表性基因有 TMTC2（p=1.63×10，R=0.656）、GLRX3（p=1.46×10，R=0.623）、DCAF15（p=2.43×10，R=0.623）、CNOT6L（p=1.46×10，R=0.609）、BSN（p=2.21×10，R=0.606）和 SENP6（p=1.59×10，R=0.604）。功能富集分析表明，相关基因主要与神经退行性疾病和癌症相关的突触传递途径有关。