Ren, C; Fang, S; Vokonas, PS; Wright, RO; Suh, H; Tucker, KL; Schwartz, J
Background: Air pollution exposure is consistently associated with harm to health, and one postulated mechanisms involves oxidative stress. If so, variants of genes related to oxidative stress may play roles in the regulation of oxidative response to air pollution. We examined whether exposure to individual air pollutants was associated with urinary 8-hydroxy-2-deoxygunosine (8-OHdG), a biomarker of oxidative stress, and then explored whether twenty candidate genes related to oxidative stress modified those associations.
Methods: We conducted this study among participants of the Normative Ageing Study during 2006-2008. We first fitted linear regression models to examine associations between individual air pollutants and 8-OHdG adjusting for a priori covariates. Then, we used a Multiple Testing Procedure (multtest in R) to identify candidate genes that significantly modified effects of the selected pollutants on 8-OHdG.
Results: 8-OHdG was significantly associated with ambient particulate matter ≤ 2.5 μm in aerodynamic diameter (PM2.5), nitrogen dioxide (NO2), maximal 1-hour ozone (O2), sulfate (SO4^2-) and organic carbon (OC), but not with black carbon (BC), carbon monoxide (CO), particle number (PN) or elemental carbon (EC). Effects were more apparent with multi-week averages of exposures. The strongest associations were with secondary pollutants: SO4^2- (29.8% (95% CI: 6.3%, 53.3%), NO (32.2% increase (95% CI: 7.4%, 56.9%), and maximal 1-hour O3 (47.7% (95% CI: 3.6%, 91.7%) per IQR increases of 21-day averages. Glutathione S-tranferase P1 (GSTP1, rs1799811), T1 and HMOX (rs2071747) significantly or marginally significantly modified associations of maximal 1-hour O3 or daily SO4^2- with 8-OHdG, with larger effects among those carrying the wild type of GSTP1, HMOX or the deletion of GSTT1.
Conclusions: Aging participants experienced an increased risk of developing oxidative DNA injury after exposure to the secondary, but not primary ambient pollutants. Variations of oxidative stress-related genes modified effects of O3 or SO4^2- on 8-OHdG. This suggests that effects of O3 or SO4^2- on 8-OHdG and other endpoints may be mediated by the oxidative stress pathway.
