Exposure to NO, CO, and PM is linked to regional DNA methylation differences in asthma.

Abstract

DNA methylation of CpG sites on genetic loci has been linked to increased risk of asthma in children exposed to elevated ambient air pollutants (AAPs). Further identification of specific CpG sites and the pollutants that are associated with methylation of these CpG sites in immune cells could impact our understanding of asthma pathophysiology. In this study, we sought to identify some CpG sites in specific genes that could be associated with asthma regulation ( and ) and to identify the different AAPs for which exposure prior to the blood draw is linked to methylation levels at these sites. We recruited subjects from Fresno, California, an area known for high levels of AAPs. Blood samples and responses to questionnaires were obtained ( = 188), and in a subset of subjects ( = 33), repeat samples were collected 2 years later. Average measures of AAPs were obtained for 1, 15, 30, 90, 180, and 365 days prior to each blood draw to estimate the short-term vs. long-term effects of the AAP exposures.Asthma was significantly associated with higher differentially methylated regions (DMRs) of the promoter region ( = 0.030) and the intronic region ( = 0.026). Additionally, at the 90-day time period (90 days prior to the blood draw), methylation was positively associated with NO, CO, and PM exposures ( = 0.001,  = 0.001, and  = 0.012, respectively). In the subset of subjects retested 2 years later ( = 33), a positive association between AAP exposure and methylation was sustained. There was also a negative correlation between the average methylation of the promoter region and activated Treg levels ( = 0.039) and a positive correlation between the average methylation of region 3 of intron 4 and cytokine expression ( = 0.030).Short-term and long-term exposures to high levels of CO, NO, and PM were associated with alterations in differentially methylated regions of . methylation showed a similar trend. For any given individual, these changes tend to be sustained over time. In addition, asthma was associated with higher differentially methylated regions of and .