Genome-wide DNA methylation analysis reveals significant impact of long-term ambient air pollution exposure on biological functions related to mitochondria and immune response

• Published in: Environmental pollution (1987) Vol. 264; p. 114707
• Main Authors: Wang, Maiqiu, Zhao, Junsheng, Wang, Yan, Mao, Ying, Zhao, Xinyi, Huang, Peng, Liu, Qiang, Ma, Yunlong, Yao, Yinghao, Yang, Zhongli, Yuan, Wenji, Cui, Wenyan, Payne, Thomas J., Li, Ming D.
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.09.2020
• Subjects: air; Air pollution; bisulfites; China; Differentially methylated region; DNA methylation; epigenetics; genes; human health; immune response; Immune system; interleukin-5; Mitochondria; WGBS; China; Air pollution; WGBS; Mitochondria; Differentially methylated region; Immune system
• ISSN: 0269-7491; 1873-6424; 1873-6424
• DOI: 10.1016/j.envpol.2020.114707

Exposure to long-term ambient air pollution is believed to have adverse effects on human health. However, the mechanisms underlying these impacts are poorly understood. DNA methylation, a crucial epigenetic modification, is susceptible to environmental factors and likely involved in these processes. We conducted a whole-genome bisulfite sequencing study on 120 participants from a highly polluted region (HPR) and a less polluted region (LPR) in China, where the HPR had much higher concentrations of five air pollutants (PM2.5, PM10, SO2, NO2, and CO) (fold difference 1.6 to 6.6 times; P value 1.80E-07 to 3.19E-23). Genome-wide methylation analysis revealed 371 DMRs in subjects from the two areas and these DMRs were located primarily in gene regulatory elements such as promoters and enhancers. Gene enrichment analysis showed that DMR-related genes were significantly enriched in diseases related to pulmonary disorders and cancers and in biological processes related to mitochondrial assembly and cytokine production. Further, HPR participants showed a higher mtDNA copy number. Of those identified DMRs, 15 were significantly correlated with mtDNA copy number. Finally, cytokine assay indicated that an increased plasma interleukin-5 level was associated with greater air pollution. Taken together, our findings suggest that exposure to long-term ambient air pollution can lead to alterations in DNA methylation whose functions relate to mitochondria and immune responses. [Display omitted] •We used whole-genome bisulfite sequencing to study the influence of air pollution on DNA methylation in blood leukocyte.•DNA methylation levels were compared between residents from two areas with distinct air quality in China.•Differentially methylated regions were enriched in gene regulatory elements.•Genes involved in mitochondrial function and immune response are preferentially impacted by air pollution. Summary: By comparing DNA methylation of subjects from two areas with distinct air quality in China, we identified differential methylation regions whose functions are mostly related to mitochondria and immune responses.