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

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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

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dc.contributor.author Ren, Cizao
dc.contributor.author Vokonas, Pantel S
dc.contributor.author Suh MacIntosh, Helen H.
dc.contributor.author Fang, Shona C.
dc.contributor.author Christiani, David C.
dc.contributor.author Schwartz, Joel David
dc.date.accessioned 2012-01-01T22:48:34Z
dc.date.issued 2010
dc.identifier.citation Ren, Cizao, Pantel S Vokonas, Helen Suh, Shona Fang, David C Christiani, and Joel Schwartz. 2010. 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. Environmental Health 9: 78. en_US
dc.identifier.issn 1476-069X en_US
dc.identifier.uri http://nrs.harvard.edu/urn-3:HUL.InstRepos:5978736
dc.description.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. en_US
dc.language.iso en_US en_US
dc.publisher BioMed Central en_US
dc.relation.isversionof doi://10.1186/1476-069X-9-78 en_US
dc.relation.hasversion http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3016327/pdf/ en_US
dash.license LAA
dc.title 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 en_US
dc.type Journal Article en_US
dc.description.version Version of Record en_US
dc.relation.journal Environmental Health en_US
dash.depositing.author Suh MacIntosh, Helen H.
dc.date.available 2012-01-01T22:48:34Z
dash.affiliation.other SPH^Environmental+Occupational Medicine+Epi en_US
dash.affiliation.other HMS^Medicine-Massachusetts General Hospital en_US
dash.affiliation.other SPH^Environmental+Occupational Medicine+Epi en_US
dash.affiliation.other HMS^Medicine-Brigham and Women's Hospital en_US
dash.affiliation.other SPH^Exposure Epidemiology and Risk Program en_US

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