DNA methylation: a potential mediator between air pollution exposures and asthma control

Exposure to air pollution is known to contribute to the development and exacerbation of asthma symptoms, impacting respiratory health through complex, not yet fully understood biological mechanisms. It is hypothesized that DNA methylation (DNAm) changes triggered by air pollutants may mediate these effects on asthma symptom control.

We aimed to investigate the effects of air pollution on DNAm in peripheral blood and asthma control. We also explored whether DNAm could potentially mediate the relationship between air pollution exposure and asthma control.

This study included 651 participants with asthma exposed to ambient air pollutants, NO₂, PM_2.5, PM₁₀, O₃, elemental carbon (EC), and NOx. Self-reported Asthma Control Test (ACT) scores for the preceding six-month period were used to assess asthma symptom control. DNAm was quantified using the Infinium HumanMethylation450 BeadChip array in whole blood and CD4 + naive T cells. An Epigenome-Wide Association Study (EWAS) was conducted to identify CpGs associated with air pollutants, with sample sizes ranging from 169 to 329. The Causal Inference Test (CIT) was employed to examine whether DNAm mediates the effects of air pollution exposure on asthma control.

Exposure to short-term PM₁₀ was associated with poorer asthma control. We identified DNA methylation changes linked to air pollution in both whole blood and CD4 + cells, with associations observed for PM₁₀, EC and NOx in whole blood, and for PM₁₀, NO₂ and PM_2.5 in CD4 + cells. Three CpG sites in whole blood-cg04605532 (p = 0.0004), cg05492904 (p = 0.0008), and cg23622322 (p = 0.001)- and one CpG in CD4 + cells -cg10022248 (p = 0.0084)-were associated with air pollution exposure and linked to asthma control. Additionally, CIT-based mediation analysis identified two CpG sites, cg02324789 (p = 0.05) and cg10758278 (p = 0.06), as potential mediators in the relationship between short-term exposure to PM₁₀ and asthma control.

These findings suggest that air pollution-associated changes in DNA methylation may affect asthma control for some loci, thus help elucidate underlying mechanisms in asthmatic patients. These epigenetic alterations highlight potential targets for understanding the pathophysiology of asthma due to air pollution. While our findings suggest possible links between air pollution, DNA methylation, and asthma control, more evidence is needed to establish causal relationships and unravel the complexities of these connections.