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.

Conclusion: 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.

Figure 1

Effects of one interquartile range increase of air pollutants on fibrinogen for exposures 4 hours, 24 hours, and 3-28 days moving average (MA₃ to MA₂₈) preceding each subject’s physical examination

Figure 2

Effects of one interquartile range increase of air pollutants on C-reactive protein for exposures 4 hours, 24 hours, and 3-28 days moving average (MA₃ to MA₂₈) preceding each subject’s physical examination

Figure 3

Effects of one interquartile range increase of air pollutants on ICAM-1 for exposures 4 hours, 24 hours, and 3-28 days moving average (MA₃ to MA₂₈) preceding each subject’s physical examination

Figure 4

Effects of one interquartile range increase of air pollutants on VCAM-1 for exposures 4 hours, 24 hours, and 3-28 days moving average (MA₃ to MA₂₈) preceding each subject’s physical examination

Figure 5

Effects of one interquartile range increase of air pollutants on blood markers according to the methylation status of repetitive elements

Figure 6

Effects of one interquartile range increase of air pollutants (3-days moving average) on blood markers according to the gene-specific methylation status and the position within the promoter region