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Co-exposure to polycyclic aromatic hydrocarbons and metals, four common polymorphisms in microRNA genes, and their gene-environment interactions: Influences on oxidative damage levels in Chinese coke oven workers
Abstract Background Human are often simultaneously exposed to polycyclic aromatic hydrocarbons (PAHs) and metals, yet relatively little is known regarding their co-exposure effects on oxidative damage. Genetic factors and the gene-environment interactions can also determine the severity of oxidative damage. Four polymorphisms in microRNA (miRNA) genes (rs11614913, rs2292832, rs2910164, and rs3746444) have been well-studied to be associated with oxidative damage-related diseases. Objective To investigate the influences of PAH-metal co-exposure, four polymorphisms, and their interactions on oxidative damage levels. Methods We conducted a cross-sectional study in 1385 coke oven workers. We quantified exposure levels of PAHs and metals by urinary monohydroxy-PAHs, plasma benzo[a]pyrene-7,8-diol-9,10-epoxide-albumin adducts, and urinary metals, respectively, and measured oxidative damage levels by 8-iso-prostaglandin-F2α and 8-hydroxydeoxyguanosine. We also genotyped four polymorphisms. Results In multiple-pollutant models, 8-iso-prostaglandin-F2α and 8-hydroxydeoxyguanosine were associated with multiple PAH exposure biomarkers, as well as with multiple metals (p trend < 0.05). Metabolites of phenanthrene and pyrene interacted synergistically with lead and zinc to influence 8-iso-prostaglandin-F2α (βinteraction > 7.75%, false discovery rate-adjusted p interaction ≤ 2.25 × 10− 5). Significantly higher 8-hydroxydeoxyguanosine was observed in carriers of rs11614913 CC variant homozygote than TC carriers (p = 0.037). Associations of the number of rs11614913 C allele with increased 8-iso-prostaglandin-F2α and 8-hydroxydeoxyguanosine were significant (βstd > 0, p trend < 0.05) and more pronounced in workers with lower metals [p for modifying effect (p ME) < 0.040]. Positive associations of some PAHs and metals with 8-iso-prostaglandin-F2α and 8-hydroxydeoxyguanosine were weaker in carriers of rs11614913 CC genotype or C allele (p ME < 0.05). Conclusion PAH-metal co-exposure, rs11614913, and their interactions may affect oxidative damage levels in Chinese population in a complex manner that are worthy of further investigation.
Graphical abstract Display Omitted
Highlights Oxidative damage levels were affected by combined effects of PAHs and of metals. PAHs interacted synergistically with metals to affect 8-iso-PGF2α. Carriers of rs11614913 CC genotype had higher 8-OH-dG than TC carriers. Rs11614913 was associated with higher damage in workers of lower urinary metals. Rs11614913 CC or C carriers had weaker positive PAH/metal-damage associations.
Co-exposure to polycyclic aromatic hydrocarbons and metals, four common polymorphisms in microRNA genes, and their gene-environment interactions: Influences on oxidative damage levels in Chinese coke oven workers
Abstract Background Human are often simultaneously exposed to polycyclic aromatic hydrocarbons (PAHs) and metals, yet relatively little is known regarding their co-exposure effects on oxidative damage. Genetic factors and the gene-environment interactions can also determine the severity of oxidative damage. Four polymorphisms in microRNA (miRNA) genes (rs11614913, rs2292832, rs2910164, and rs3746444) have been well-studied to be associated with oxidative damage-related diseases. Objective To investigate the influences of PAH-metal co-exposure, four polymorphisms, and their interactions on oxidative damage levels. Methods We conducted a cross-sectional study in 1385 coke oven workers. We quantified exposure levels of PAHs and metals by urinary monohydroxy-PAHs, plasma benzo[a]pyrene-7,8-diol-9,10-epoxide-albumin adducts, and urinary metals, respectively, and measured oxidative damage levels by 8-iso-prostaglandin-F2α and 8-hydroxydeoxyguanosine. We also genotyped four polymorphisms. Results In multiple-pollutant models, 8-iso-prostaglandin-F2α and 8-hydroxydeoxyguanosine were associated with multiple PAH exposure biomarkers, as well as with multiple metals (p trend < 0.05). Metabolites of phenanthrene and pyrene interacted synergistically with lead and zinc to influence 8-iso-prostaglandin-F2α (βinteraction > 7.75%, false discovery rate-adjusted p interaction ≤ 2.25 × 10− 5). Significantly higher 8-hydroxydeoxyguanosine was observed in carriers of rs11614913 CC variant homozygote than TC carriers (p = 0.037). Associations of the number of rs11614913 C allele with increased 8-iso-prostaglandin-F2α and 8-hydroxydeoxyguanosine were significant (βstd > 0, p trend < 0.05) and more pronounced in workers with lower metals [p for modifying effect (p ME) < 0.040]. Positive associations of some PAHs and metals with 8-iso-prostaglandin-F2α and 8-hydroxydeoxyguanosine were weaker in carriers of rs11614913 CC genotype or C allele (p ME < 0.05). Conclusion PAH-metal co-exposure, rs11614913, and their interactions may affect oxidative damage levels in Chinese population in a complex manner that are worthy of further investigation.
Graphical abstract Display Omitted
Highlights Oxidative damage levels were affected by combined effects of PAHs and of metals. PAHs interacted synergistically with metals to affect 8-iso-PGF2α. Carriers of rs11614913 CC genotype had higher 8-OH-dG than TC carriers. Rs11614913 was associated with higher damage in workers of lower urinary metals. Rs11614913 CC or C carriers had weaker positive PAH/metal-damage associations.
Co-exposure to polycyclic aromatic hydrocarbons and metals, four common polymorphisms in microRNA genes, and their gene-environment interactions: Influences on oxidative damage levels in Chinese coke oven workers
Xie, Yunling (author) / Lin, Tao (author) / Yang, Ming (author) / Zhang, Zhaorui (author) / Deng, Na (author) / Tang, Mengqi (author) / Xiao, Yongmei (author) / Guo, Huan (author) / Deng, Qifei (author)
2019-07-23
Article (Journal)
Electronic Resource
English
PAHs , polycyclic aromatic hydrocarbons , PM , particulate matter , ROS , reactive oxygen species , miRNA , microRNA , COEs , coke oven emissions , SNP , single nucleotide polymorphisms , 8-iso-PGF2<italic>α</italic> , 8-iso-prostaglandin-F2<italic>α</italic> , 8-OH-dG , 8-hydroxydeoxyguanosine , BMI , body mass index , OH-PAH , monohydroxy-PAH , OH-Nap , hydroxynaphthalene , OH-Flu , hydroxyfluorene , OH-Phe , hydroxyphenanthrene , 1-OH-Pyr , 1-hydroxypyrene , LOQ , limits of quantification , CV , coefficients of variation , ∑OH-Nap , the sum of 1- and 2-hydroxynaphthalene , ∑OH-Flu , the sum of 2- and 9-hydroxyfluorene , ∑OH-Phe , the sum of 1-, 2-, 3-, 4-, and 9-hydroxyphenanthrene , BPDE-Alb adducts , benzo[<italic>a</italic>]pyrene-7,8-diol-9,10-epoxide-albumin adducts , ELISA , sandwich enzyme-linked immunosorbent assay , ln-transformed , natural logarithm-transformed , FDR , false discovery rate , LASSO , least absolute shrinkage and selection operator , MSE , mean squared error , β<inf>interaction</inf> , regression coefficient of interaction term , HWE , Hardy-Weinberg equilibrium , <italic>p</italic> <inf>ME</inf> , <italic>p</italic> values for modifying effect , Co-exposure , Polycyclic aromatic hydrocarbons , Metals , Rs11614913 , Interaction , Oxidative damage