The association between cumulative exposure to PM2.5 and DNA methylation measured using methyl-capture sequencing
Hyun Woo Ji1, Jieun Kang2, Hwan-Cheol Kim3
1Division of Pulmonology, Department of Internal Medicine, National Health Insurance Service Ilsan Hospital, Goyang, Republic of Korea.
Background:
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.
Methods:
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.
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 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.
Gov Identifier:
NCT04878367.
Insights
Exposure to fine particulate matter (PM2.5) significantly alters DNA methylation in chronic obstructive pulmonary disease patients. Mid-term exposure showed the highest impact on DNA methylation, linking to neurodegenerative diseases and cancer pathways.
Area of Science:
- Environmental Health
- Molecular Biology
- Genomics
Background:
- Particulate matter (PM2.5) is known to influence gene regulation through DNA methylation.
- The precise mechanisms by which PM2.5 affects DNA methylation remain unclear.
- This study investigates the link between personal PM2.5 exposure and DNA methylation in CpG islands.
Purpose of the Study:
- To examine the association between personal PM2.5 exposure and DNA methylation patterns.
- To identify gene pathways affected by PM2.5-induced DNA methylation.
- To explore the relationship in patients with chronic obstructive pulmonary disease (COPD).
Main Methods:
- 95 male COPD patients were monitored for 12 months.
- Individual PM2.5 exposure was assessed over short-term (7 days), mid-term (35 days), and long-term (90 days).
- DNA methylation analysis was performed on blood samples using Illumina NovaSeq 6000, followed by mixed-effects modeling and functional enrichment analysis.
Main Results:
- Differential methylation was observed at numerous CpG sites, varying with exposure duration and model type.
- Key genes such as TMTC2, GLRX3, DCAF15, CNOT6L, BSN, and SENP6 showed significant associations with PM2.5 exposure.
- Functional analysis linked these genes to pathways involved in synaptic transmission in neurodegenerative diseases and cancer.
Conclusions:
- A significant association exists between PM2.5 exposure and DNA methylation, particularly evident with short-term exposure.
- Mid-term PM2.5 exposure demonstrated the most substantial impact on DNA methylation levels.
- The study identified pathways related to neurodegenerative diseases and cancer as being associated with PM2.5 exposure in COPD patients.
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