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

BACKGROUND AND OBJECTIVES: We have previously shown that reduced defenses against oxidative stress due to glutathione S-transferase M 1 (GSTM1) deletion modify the effects of PM2.5 (fine-particulate air pollution of < 2.5 mu m, 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 PM2.5 concentrations in the 48 hr preceding HRV measurement, controlling for confounders and a random subject effect. RESULTS: PM2.5 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 PM2.5 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 mu g/m(3) increase in PM. CONCLUSIONS: Oxidative stress is an important pathway for the autonomic effects of particles.