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.
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.
复制标题
DOI：
10.1186/1476-069x-9-78
复制
发表时间：
2010-12-07
期刊：
影响因子：
--
通讯作者：
Schwartz J
中科院分区：
文献类型：
--
作者：
Ren C;Vokonas PS;Suh H;Fang S;Christiani DC;Schwartz J
空气污染与有害的人类健康有关，但污染产生影响的机制仍有待澄清。一种建议的途径是污染导致氧化应激。如果是这样的话，氧化应激相关基因型可能会改变氧化反应防御污染暴露。我们通过检测一系列氧化应激相关基因（20个单核苷酸多态性，9个基因中的SNP）是否改变了污染物（有机碳（OC），臭氧和硫酸盐）与尿8-羟基-2-脱氧鸟苷（8-OHdG）的关系来探索潜在的途径，8-OHdG是320名老年男性中氧化应激的生物标志物。我们使用了由我们团队修改的R中的多重检验程序来确定候选基因对先验协变量的调整的显著性。我们发现，谷胱甘肽S-转移酶P1（GSTP 1，rs 1799811），M1和过氧化氢酶（rs 2284367）和组特异性组分（GC，rs 2282679，rs 1155563）显着或轻微显着修改OC和/或硫酸盐的影响，其中携带野生型GSTP 1，过氧化氢酶，非野生型GC和非空GSTM 1的影响更大。氧化应激相关基因的多态性改变了OC和/或硫酸盐对8-OHdG的影响，表明OC或硫酸盐对8-OHdG和其他终点的影响可能是通过氧化应激途径。
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. 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. 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. 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.