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

Marie Abele Bind, Johanna Lepeule, Antonella Zanobetti, Antonio Gasparrini, Andrea Baccarelli, Brent A. Coull, Letizia Tarantini, Pantel S. Vokonas, Petros Koutrakis, Joel Schwartz

Research output: Contribution to journalArticlepeer-review


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 and components of fine particle mass are associated with changes in methylation on tissue factor (F3), interferon gamma (IFN-γ), interleukin 6 (IL- 6), toll-like receptor 2 (TLR-2), and intercellular adhesion molecule 1 (ICAM-1). We investigated associations between air pollution exposure and gene-specific methylation in 777 elderly men participating in the Normative Aging Study (1999- 2009). We repeatedly measured methylation at multiple CpG sites within each gene's promoter region and calculated the mean of the position-specific measurements. We examined intermediate-term associations between primary and secondary air pollutants and mean methylation and methylation at each position with distributed-lag models. Increase in air pollutants concentrations was significantly associated with F3, ICAM-1, and TLR-2 hypomethylation, and IFN-γ and IL-6 hypermethylation. An interquartile range increase in black carbon concentration averaged over the four weeks prior to assessment was associated with a 12% reduction in F3 methylation (95% CI: -17% to -6%). For some genes, the change in methylation was observed only at specific locations within the promoter region. DNA methylation may reflect biological impact of air pollution. We found some significant mediated effects of black carbon on fibrinogen through a decrease in F3 methylation, and of sulfate and ozone on ICA M-1 protein through a decrease in ICAM-1 methylation.

Original languageEnglish
Pages (from-to)448-458
Number of pages11
Issue number3
Publication statusPublished - Jan 2 2014


  • Air pollution
  • Effect modification
  • Elderly
  • Gene-specific DNA methylation
  • Mediation analysis
  • Traffic

ASJC Scopus subject areas

  • Cancer Research
  • Molecular Biology


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