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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.

Authors
Ren-C; Vokonas-PS; Suh-H; Fang-S; Christiani-DC; Schwartz-J
Source
Environ Health Glob Access Sci Source 2010 Dec; 9:78
NIOSHTIC No.
20038491
Abstract
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.
Keywords
Airborne-particles; Air-quality-measurement; Biochemical-analysis; Biodynamics; Biological-effects; Biological-factors; Environmental-exposure; Epidemiology; Exposure-assessment; Genes; Genetic-factors; Indoor-air-pollution; Indoor-environmental-quality; Mathematical-models; Oxidation; Oxidative-metabolism; Oxidative-processes; Pollutants; Pollution; Quantitative-analysis; Risk-factors; Statistical-analysis; Stress
Contact
Cizao Ren, Exposure, Epidemiology, and Risk Program, Department of Environmental Health, Harvard School of Public Health, 665 Huntington Avenue, Boston, MA 02115
Publication Date
20101207
Document Type
Journal Article
Email Address
rencizao@yahoo.com
Funding Type
Grant
Fiscal Year
2011
NTIS Accession No.
NTIS Price
Identifying No.
Grant-Number-T42-OH-008416
ISSN
1476-069X
Source Name
Environmental Health: A Global Access Science Source
State
MA
Performing Organization
Harvard School of Public Health
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