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.
Exposure, Epidemiology, and Risk Program, Department of Environmental Health, Harvard School of Public Health, Boston, MA, USA. rencizao@yahoo.com
Cizao
C
Ren
Pantel S
PS
Vokonas
Helen
H
Suh
Shona
S
Fang
David C
DC
Christiani
Joel
J
Schwartz
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000368:Aged; D000369:Aged, 80 and over; D000397:Air Pollution; D002244:Carbon / Q000633:toxicity; D015331:Cohort Studies; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000235:genetics / Q000652:urine; D004781:Environmental Exposure / Q000009:adverse effects; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008404:Massachusetts; D008875:Middle Aged; D018384:Oxidative Stress; D010126:Ozone / Q000633:toxicity; D052638:Particulate Matter / Q000009:adverse effects*; D020641:Polymorphism, Single Nucleotide; D013431:Sulfates / Q000633:toxicity
D052638:Particulate Matter; D013431:Sulfates; D010126:Ozone; D002244:Carbon; D000080242:8-Hydroxy-2'-Deoxyguanosine; D003849:Deoxyguanosine