Air pollution and gene-specific methylation in the Normative Aging Study: Association, effect modification, and mediation analysis

摘要: The mechanisms by which air pollution has multiple systemic effects in humans are not fully elucidated, but appear to include inflammation and thrombosis. This study examines whether concentrations of ozone components fine particle mass associated with changes methylation on tissue factor (F3), interferon gamma (IFN-γ), interleukin 6 (IL-6), toll-like receptor 2 (TLR-2), intercellular adhesion molecule 1 (ICAM-1). We investigated associations between exposure gene-specific 777 elderly men participating the Normative Aging Study (1999-2009). repeatedly measured at CpG sites within each gene's promoter region calculated mean position-specific measurements. examined intermediate-term primary secondary pollutants position distributed-lag models. Increase was significantly F3, ICAM-1, TLR-2 hypomethylation, IFN-γ IL-6 hypermethylation. An interquartile range increase black carbon concentration averaged over four weeks prior assessment a 12% reduction F3 (95% CI: -17% -6%). For some genes, change observed only specific locations region. DNA may reflect biological impact pollution. found significant mediated fibrinogen through decrease methylation, sulfate ICAM-1 protein methylation.