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

BACKGROUND: Air pollution is associated with adverse human health, but mechanisms through which pollution exerts effects remain to be clarified. One suggested pathway is that pollution causes oxidative stress. If so, oxidative stress-related genotypes may modify the oxidative response defenses to pollution exposure. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.National Institute of Environmental Health Sciences (ES014663, ES 15172, and ES-00002); United States Environmental Protection Agency (R832416); United States Department of Agriculture (58-1950-7-707); Cooperative Studies Program/Epidemiology Research and Information Center of the U.S. Department of Veterans Affairs; Massachusetts Veterans Epidemiology Research and Information Center; Harvard-NIOSH ERC Pilot (T42 OH008416