Effect modification of air pollution on Urinary 8-Hydroxy-2'-Deoxyguanosine by genotypes: an application of the multiple testing procedure to identify significant SNP interactions

We explored the potential pathway by examining whether an array of oxidative stress-related genes (twenty single nucleotide polymorphisms, SNPs in nine genes) modified associations of pollutants (organic carbon (OC), ozone and sulfate) with urinary 8-hydroxy-2-deoxygunosine (8-OHdG), a biomarker of oxidative stress among the 320 aging men. We used a Multiple Testing Procedure in R modified by our team to identify the significance of the candidate genes adjusting for a priori covariates.We found that glutathione S-tranferase P1 (GSTP1, rs1799811), M1 and catalase (rs2284367) and group-specific component (GC, rs2282679, rs1155563) significantly or marginally significantly modified effects of OC and/or sulfate with larger effects among those carrying the wild type of GSTP1, catalase, non-wild type of GC and the non-null of GSTM1.Polymorphisms of oxidative stress-related genes modified effects of OC and/or sulfate on 8-OHdG, suggesting that effects of OC or sulfate on 8-OHdG and other endpoints may be through the oxidative stress pathway.Many studies have shown that ambient pollution is consistently associated with adverse health outcomes [1-6], but mechanisms accountable for these associations have not been fully elucidated. Suggested biological mechanisms linking air pollution and cardiovascular diseases include direct effect on the myocardium, disturbance of the cardiac autonomic nervous system, pulmonary and systematic oxidative stress and inflammatory response that triggers endothelial dysfunction, atherosclerosis and coagulation/thrombosis [7]. Understanding relative roles of such potential is a priority of recent air pollution epidemiology.Some studies have demonstrated that exposures to particulate matter (aerodynamic diameter ≤2.5 μm, PM2.5) and ozone are associated with global oxidative stress [7-11]. Others reported that the exposures were associated with heart rate variability (HRV), plasma homocysteine and C-reactive protein and such effects were modified b