Particulate air pollution, oxidative stress genes, and heart rate variability in an elderly cohort

Environ Health Perspect. 2007 Nov;115(11):1617-22. doi: 10.1289/ehp.10318.


Background and objectives: 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.

Keywords: GST; HMOX-1; PM2.5; air particles; air pollution; cardiovascular health; genetic variation; heart rate variability.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Air Pollutants / adverse effects
  • Air Pollution / adverse effects*
  • Cohort Studies
  • Genetic Variation*
  • Glutathione Transferase / genetics*
  • Heart Rate / physiology*
  • Heme Oxygenase-1 / genetics*
  • Humans
  • Male
  • Microsatellite Repeats / genetics
  • Oxidative Stress / genetics*
  • Particulate Matter / adverse effects*
  • Polymorphism, Genetic


  • Air Pollutants
  • Particulate Matter
  • HMOX1 protein, human
  • Heme Oxygenase-1
  • Glutathione Transferase