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

Details

• Alternative Title:
  Environ Health
• Personal Author:
  Ren, Cizao ; Vokonas, Pantel S ; Suh, Helen ; Fang, Shona ; Christiani, David C ; Schwartz, Joel
• Description:
  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.
  
  
• Subjects:
  Aged Aged, 80 And Over Air Pollution Carbon Cohort Studies Deoxyguanosine Environmental Exposure Humans Longitudinal Studies Male Middle Aged Oxidative Stress Ozone Particulate Matter Polymorphism, Single Nucleotide Sulfates

  More +
• Source:
  Environ Health. 2010; 9:78.
• Pubmed ID:
  21138591
• Pubmed Central ID:
  PMC3016327
• Document Type:
  Journal Article
• Funding:
  ES 15172/ES/NIEHS NIH HHS/United States ; ES-00002/ES/NIEHS NIH HHS/United States ; ES014663/ES/NIEHS NIH HHS/United States ; T42 OH008416/OH/NIOSH CDC HHS/United States
• Place as Subject:
  Massachusetts
• Volume:
  9
• NIOSHTIC Number:
  nn:20038491
• Collection(s):
  CDC Public Access National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:7a7184c06bd7057c4e23d5094fe6862bddcd96e940db22541ca08dde92abe1f1bdc99ea98eb2c6ccf92a14b4b867d75298139dadb0f11762380b89842ab40331
• Download URL:
  https://stacks.cdc.gov/view/cdc/22841/cdc_22841_DS1.pdf
• File Type:
  [PDF - 287.47 KB ]