Dissecting the pathogenic effects of ambient air pollution exposure and its blood DNA methylation markers on cardiovascular disease risk.

BACKGROUND

Cardiovascular diseases (CVD) are influenced by a number of factors, including environmental and genetic components. By linking prospective cohort studies with epigenetics and CVD outcomes, it may be possible to gain insight into the complex mechanisms underlying CVD. This study aims to evaluate the impact of air pollution on CVD and investigate whether DNA methylation (DNAm) mediates the association between air pollution and CVD.

METHODS

In the prospective cohort study, the relationship between air pollutants and CVD incidence was analyzed using Cox regression. Dose-response was assessed by the restricted cubic spline model, and multiple pollutants' impact was evaluated by the weighted quantile sum model. The link between genetically predicted DNAm sites related to air pollutants and CVD risk was explored through epigenetic Mendelian randomization (MR), with further evidence provided by gene colocalization analysis.

RESULTS

For every 10 μg/m3 increase, particulate matter with diameters less than 2.5 μm (PM2.5), particulate matter with diameter less than 10 μm (PM10), nitrogen dioxide (NO2), and sulfur dioxide (SO2) increased the risk of CVD by 6.2%, 4.4%, 9.3%, and 6.1%, respectively, with all showing a linear association. Of the four air pollutants, PM10 and PM2.5 were identified as the most significant contributors to the CVD risk, accounting for 61% and 20%, respectively. Genetically predicted methylation at the PM2.5-related CpG site cg01065697 was linked to a higher risk of myocardial infarction (MI) and coronary heart disease (CHD), the NO2-related CpG site cg07091220 was associated with increased MI risk, the NO2-related sites cg15474579, cg16348358, and cg19869422 were linked to a higher risk of heart failure (HF).

CONCLUSION

Our study confirms a significant association between air pollution, DNAm and CVD risk, and provides new insights into the pathogenic effects of air pollution on CVD.