Long-term ambient fine particulate matter and DNA methylation in inflammation pathways: results from the Sister Study

Although underlying mechanisms of long-term exposure to air pollution and cardiovascular disease remain obscure, effects might partially act through changes in DNA methylation. We examined the associations between long-term ambient fine particulate matter (PM_2.5) and methylation, considering both a global measure and methylation at several specific inflammation-related loci, in two random sub-cohorts selected from a nationwide prospective study of US women. In one sub-cohort we measured long interspersed nucleotide element (LINE-1); in the other, we measured methylation at three candidates CpG loci related to inflammatory pathways [tumour necrosis factor-alpha (TNF-α) and toll-like receptor-2 (TLR-2)]. Annual average contemporaneous ambient PM_2.5 concentrations were estimated for the current residence. We used both classical least-squares and quantile regression models to estimate the long-term effects. The women in sub-cohorts 1 (n = 491) and 2 (n = 882) had mean ages of 55.8 and 56.7, respectively. Neither modelling approach showed an association between long-term PM_2.5 and LINE-1 methylation or between PM_2.5 and either of the two CpG sites in TLR-2. Using linear regression, there was an estimated change of -6.5% (95% confidence interval CI: -13.34%, 0.35%) in mean methylation of TNF-α per 5 µg/m³ increase in PM_2.5. Quantile regression showed that the downward shift was mainly in the lower half of the distribution of DNA methylation. Long-term residence in regions with higher ambient PM_2.5 may be associated with increased TNF-α through a reduction in methylation, particularly in the lower tail. Epigenetic markers and quantile regression might provide insight into mechanisms underlying the relationship between air pollution and cardiovascular disease.