title: Particulate air pollution, oxidative stress genes, and heart rate variability in an elderly cohort.
abstract: OBJECTIVE
  We have previously shown that reduced defenses against oxidative stress due to glutathione S-transferase M1 (GSTM1) deletion modify the effects of PM(2.5) (fine-particulate air pollution of < 2.5 microm in aerodynamic diameter) on heart rate variability (HRV) in a cross-sectional analysis of the Normative Aging Study, an elderly cohort. We have extended this to include a longitudinal analysis with more subjects and examination of the GT short tandem repeat polymorphism in the heme oxygenase-1 (HMOX-1) promoter.
  
  
  METHODS
  HRV measurements were taken on 539 subjects. Linear mixed effects models were fit for the logarithm of HRV metrics-including standard deviation of normal-to-normal intervals (SDNN), high frequency (HF), and low frequency (LF)-and PM(2.5) concentrations in the 48 hr preceding HRV measurement, controlling for confounders and a random subject effect.
  
  
  RESULTS
  PM(2.5) was significantly associated with SDNN (p = 0.04) and HF (p = 0.03) in all subjects. There was no association in subjects with GSTM1, whereas there was a significant association with SDNN, HF, and LF in subjects with the deletion. Similarly, there was no association with any HRV measure in subjects with the short repeat variant of HMOX-1, and significant associations in subjects with any long repeat. We found a significant three-way interaction of PM(2.5) with GSTM1 and HMOX-1 determining SDNN (p = 0.008), HF (p = 0.01) and LF (p = 0.04). In subjects with the GSTM1 deletion and the HMOX-1 long repeat, SDNN decreased by 13% [95% confidence interval (CI), -21% to -4%], HF decreased by 28% (95% CI, -43% to -9%), and LF decreased by 20% (95% CI, -35% to -3%) per 10 microg/m(3) increase in PM.
  
  
  CONCLUSIONS
  Oxidative stress is an important pathway for the autonomic effects of particles.
authors.affiliation: Department of Environmental Health, Harvard School of Public Health, Boston, Massachusetts 02215, USA.
authors.forename: Teresa
authors.initials: T
authors.lastname: Chahine
authors.forename: Andrea
authors.initials: A
authors.lastname: Baccarelli
authors.forename: Augusto
authors.initials: A
authors.lastname: Litonjua
authors.forename: Robert O
authors.initials: RO
authors.lastname: Wright
authors.forename: Helen
authors.initials: H
authors.lastname: Suh
authors.forename: Diane R
authors.initials: DR
authors.lastname: Gold
authors.forename: David
authors.initials: D
authors.lastname: Sparrow
authors.forename: Pantel
authors.initials: P
authors.lastname: Vokonas
authors.forename: Joel
authors.initials: J
authors.lastname: Schwartz
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000393:Air Pollutants / Q000009:adverse effects; D000397:Air Pollution / Q000009:adverse effects*; D015331:Cohort Studies; D014644:Genetic Variation; D005982:Glutathione Transferase / Q000235:genetics*; D006339:Heart Rate / Q000502:physiology*; D051547:Heme Oxygenase-1 / Q000235:genetics*; D006801:Humans; D008297:Male; D018895:Microsatellite Repeats / Q000235:genetics; D018384:Oxidative Stress / Q000235:genetics*; D052638:Particulate Matter / Q000009:adverse effects*; D011110:Polymorphism, Genetic
chemical_list: D000393:Air Pollutants; D052638:Particulate Matter; C496541:HMOX1 protein, human; D051547:Heme Oxygenase-1; D005982:Glutathione Transferase