title: Epigenetic influences on associations between air pollutants and lung function in elderly men: the normative aging study.
abstract: BACKGROUND
  Few studies have been performed on pulmonary effects of air pollution in the elderly--a vulnerable population with low reserve capacity--and mechanisms and susceptibility factors for potential effects are unclear.
  
  
  OBJECTIVE
  We evaluated the lag structure of air pollutant associations with lung function and potential effect modification by DNA methylation (< or ≥ median) at 26 individual CpG sites in nine candidate genes in a well-characterized cohort of elderly men.
  
  
  METHODS
  We measured forced vital capacity (FVC), forced expiratory volume in 1 sec (FEV1), and blood DNA methylation one to four times between 1999 and 2009 in 776 men from the Normative Aging Study. Air pollution was measured at fixed monitors 4 hr to 28 days before lung function tests. We used linear mixed-effects models to estimate the main effects of air pollutants and effect modification by DNA methylation.
  
  
  RESULTS
  An interquartile range (IQR) increase in subchronic exposure (3 to 28 days cumulated), but not in acute exposure (during the previous 4 hr, or the current or previous day), to black carbon, total and nontraffic particles with aerodynamic diameter ≤ 2.5 μm (PM2.5), carbon monoxide, and nitrogen dioxide was associated with a 1-5% decrease in FVC and FEV1 (p < 0.05). Slope estimates were greater for FVC than FEV1, and increased with cumulative exposure. The estimates slopes for air pollutants (28 days cumulated) were higher in participants with low (< median) methylation in TLR2 at position 2 and position 5 and high (≥ median) methylation in GCR.
  
  
  CONCLUSIONS
  Subchronic exposure to traffic-related pollutants was associated with significantly reduced lung function in the elderly; nontraffic pollutants (particles, ozone) had weaker associations. Epigenetic mechanisms related to inflammation and immunity may influence these associations.
authors.affiliation: Exposure, Epidemiology, and Risk Program, Department of Environmental Health, Harvard School of Public Health, Boston, Massachusetts, USA.
authors.forename: Johanna
authors.initials: J
authors.lastname: Lepeule
authors.forename: Marie-Abele Catherine
authors.initials: MA
authors.lastname: Bind
authors.forename: Andrea A
authors.initials: AA
authors.lastname: Baccarelli
authors.forename: Petros
authors.initials: P
authors.lastname: Koutrakis
authors.forename: Letizia
authors.initials: L
authors.lastname: Tarantini
authors.forename: Augusto
authors.initials: A
authors.lastname: Litonjua
authors.forename: David
authors.initials: D
authors.lastname: Sparrow
authors.forename: Pantel
authors.initials: P
authors.lastname: Vokonas
authors.forename: Joel D
authors.initials: JD
authors.lastname: Schwartz
mesh_terms: D000368:Aged; D000393:Air Pollutants / Q000633:toxicity*; D000397:Air Pollution / Q000706:statistics & numerical data*; D019175:DNA Methylation; D004781:Environmental Exposure / Q000706:statistics & numerical data*; D044127:Epigenesis, Genetic; D057890:Epigenomics; D005541:Forced Expiratory Volume; D006801:Humans; D008297:Male; D008404:Massachusetts; D052638:Particulate Matter / Q000009:adverse effects*; D012129:Respiratory Function Tests; D012143:Respiratory Physiological Phenomena
chemical_list: D000393:Air Pollutants; D052638:Particulate Matter