title: Air pollution and markers of coagulation, inflammation, and endothelial function: associations and epigene-environment interactions in an elderly cohort.
abstract: BACKGROUND
  Previous studies suggest that air pollution is related to thrombosis, inflammation, and endothelial dysfunction. Mechanisms and sources of susceptibility are still unclear. One possibility is that these associations can be modified by DNA methylation states.
  
  
  METHODS
  We conducted a cohort study with repeated measurements of fibrinogen, C-reactive protein, intercellular adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule-1 (VCAM-1) in 704 elderly men participating in the Veterans Administration Normative Aging Study (2000-2009). We investigated short- and intermediate-term air pollution effects on these blood markers, and epigene-environment interactions by DNA methylation of Alu, LINE-1, tissue factor (F3), Toll-like receptor 2 (TLR-2), and ICAM-1.
  
  
  RESULTS
  We found effects of particle number, black carbon, nitrogen dioxide (NO(2)), and carbon monoxide (CO) on fibrinogen. Ozone was a predictor of C-reactive protein and ICAM-1. Particle number, black carbon, NO(2), CO, PM(2.5), and sulfates were associated with ICAM-1 and VCAM-1. An interquartile range increase in 24-hour exposure for NO(2) was associated with a 1.7% (95% confidence interval = 0.2%-3.3%) increase in fibrinogen for ozone; a 10.8% (2.2%-20.0%) increase in C-reactive protein for particle number; a 5.9% (3.6%-8.3%) increase in ICAM-1; and for PM(2.5), a 3.7% (1.7%-5.8%) increase in VCAM-1. The air pollution effect was stronger among subjects having higher Alu, lower LINE-1, tissue factor, or TLR-2 methylation status.
  
  
  CONCLUSIONS
  We observed associations of traffic-related pollutants on fibrinogen, and both traffic and secondary particles on C-reactive protein, ICAM-1, and VCAM-1. There was effect modification by DNA methylation status, indicating that epigenetic states can convey susceptibility to air pollution.
authors.affiliation: Exposure, Epidemiology, and Risk Program, Department of Environmental Health, Harvard School of Public Health, Boston, MA 02115, USA. mbind@hsph.harvard.edu
authors.forename: Marie-Abele
authors.initials: MA
authors.lastname: Bind
authors.forename: Andrea
authors.initials: A
authors.lastname: Baccarelli
authors.forename: Antonella
authors.initials: A
authors.lastname: Zanobetti
authors.forename: Letizia
authors.initials: L
authors.lastname: Tarantini
authors.forename: Helen
authors.initials: H
authors.lastname: Suh
authors.forename: Pantel
authors.initials: P
authors.lastname: Vokonas
authors.forename: Joel
authors.initials: J
authors.lastname: Schwartz
mesh_terms: D000368:Aged; D000397:Air Pollution / Q000009:adverse effects*; D015415:Biomarkers / Q000097:blood; D001778:Blood Coagulation Disorders / Q000097:blood / Q000139:chemically induced* / Q000235:genetics; D002097:C-Reactive Protein / Q000032:analysis; D002244:Carbon / Q000009:adverse effects; D002248:Carbon Monoxide / Q000009:adverse effects; D019175:DNA Methylation / Q000187:drug effects; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000503:physiopathology; D044127:Epigenesis, Genetic; D005340:Fibrinogen / Q000032:analysis; D059647:Gene-Environment Interaction; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000139:chemically induced* / Q000235:genetics; D018799:Intercellular Adhesion Molecule-1 / Q000097:blood; D008297:Male; D009585:Nitrogen Dioxide / Q000009:adverse effects; D010126:Ozone / Q000009:adverse effects; D052638:Particulate Matter / Q000009:adverse effects; D011446:Prospective Studies; D019010:Vascular Cell Adhesion Molecule-1 / Q000097:blood; D014652:Vascular Diseases / Q000097:blood / Q000139:chemically induced* / Q000235:genetics
chemical_list: D015415:Biomarkers; D052638:Particulate Matter; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D010126:Ozone; D002244:Carbon; D002248:Carbon Monoxide; D005340:Fibrinogen; D002097:C-Reactive Protein; D009585:Nitrogen Dioxide