연구성과 홍보

Respir Res. 2024 Sep 9;25(1):335.

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

Authors : Hyun Woo Ji1, Jieun Kang2, Hwan-Cheol Kim3, Junghee Jung4, Seon-Jin Lee5, Ji Ye Jung6*, Sei Won Lee7

Affiliations :

1Division of Pulmonology, Department of Internal Medicine, National Health Insurance Service Ilsan Hospital, Goyang, Republic of Korea.

2Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Ilsan Paik Hospital, Inje University College of Medicine, Goyang, Republic of Korea.

3Department of Occupational and Environmental Medicine, Inha University College of Medicine, Incheon, Republic of Korea.

4Macrogen Inc., Seoul, Republic of Korea.

5Environmental Disease Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, Republic of Korea.

6Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea.

7Department of Pulmonary and Critical Care Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.

DOI: 10.1186/s12931-024-02955-3.

Abstract :

Background: Particulate matter with a diameter of < 2.5 μm (PM_2.5) influences gene regulation via DNA methylation; however, its precise mechanism of action remains unclear. Thus, this study aimed to examine the connection between personal PM_2.5 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_2.5 concentrations were measured for 12 months, with individual exposure recorded for 24 h every 3 months. Mean indoor and estimated individual PM_2.5 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 PM_2.5 exposure and CpG methylation sites was confirmed via a mixed-effects model. Functional enrichment analysis was performed on unique CpG methylation sites associated with PM_2.5 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 × 10-3, 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.

Conclusion: A significant association was observed between PM_2.5 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.