Abstract
BACKGROUND: Asthma gene DNA methylation may underlie the effects of air pollution on airway inflammation. However, the temporality and individual susceptibility to environmental epigenetic regulation of asthma has not been fully elucidated. Our objective was to determine the timeline of black carbon (BC) exposure, measured by personal sampling, on DNA methylation of allergic asthma genes 5 days later to capture usual weather variations and differences related to changes in behavior and activities. We also sought to determine how methylation may vary by seroatopy and cockroach sensitization and by elevated fractional exhaled nitric oxide (FeNO). METHODS: Personal BC levels were measured during two 24-h periods over a 6-day sampling period in 163 New York City children (age 9-14 years), repeated 6 months later. During home visits, buccal cells were collected as noninvasive surrogates for lower airway epithelial cells and FeNO measured as an indicator of airway inflammation. CpG promoter loci of allergic asthma genes (e.g., interleukin 4 (IL4), interferon gamma (IFNγ), inducible nitric oxide synthase (NOS2A)), arginase 2 (ARG2)) were pyrosequenced at the start and end of each sampling period. RESULTS: Higher levels of BC were associated with lower methylation of IL4 promoter CpG(-48) 5 days later. The magnitude of association between BC exposure and demethylation of IL4 CpG(-48) and NOS2A CpG(+5099) measured 5 days later appeared to be greater among seroatopic children, especially those sensitized to cockroach allergens (RR [95% CI] 0.55 [0.37-0.82] and 0.67 [0.45-0.98] for IL4 CpG(-48) and NOS2A CpG(+5099), respectively), compared to non-sensitized children (RR [95% CI] 0.87 [0.65-1.17] and 0.95 [0.69-1.33] for IL4 CpG(-48) and NOS2A CpG(+5099), respectively); however, the difference was not statistically different. In multivariable linear regression models, lower DNA methylation of IL4 CpG(-48) and NOS2A CpG(+5099) were associated with increased FeNO. CONCLUSIONS: Our results suggest that exposure to BC may exert asthma proinflammatory gene demethylation 5 days later that in turn may link to airway inflammation. Our results further suggest that seroatopic children, especially those sensitized to cockroach allergens, may be more susceptible to the effect of acute BC exposure on epigenetic changes.