Associations Of MicroRNA Genetic Variants And Polycyclic Aromatic Hydrocarbons Exposure With Coke Oven Workers’ Oxidative Stress

Objective1.Investigate the effect of occupational Polycyclic aromatic hydrocarbons（PAHs）exposure on the level of oxidative stress and antioxidant capacity in coke oven workers,and evaluate the benchmark dose（BMD）of PAHs that can induce oxidative damage.2.Explore the associations of microRNA genetic variants,and their interactions with polycyclic aromatic hydrocarbons with the levels of plasma oxidative stress and antioxidant capacity.Subjects and Methods1 Subjects A total of 542 coke oven workers from a steelwork and 235 office teachers and service staffs in the same city were recruited.2 Research methods The concentrations of 4 urine OH-PAHs were detected with Ultra Performance Liquid Chromatography（UPLC）.Soxhlet extractor methods were used to detect the concentration of coke oven emissions in the air.Different kinds of agent kits were used to detect the level of total antioxidant capacity（T-AOC）,catalase（CAT）,malondialdehyde（MDA）and hydrogen peroxide（H2O2）in plasma.Matrix-Assisted Laser Desorption/Ionization Time of Flight Mass Spectrometry（MALDI-TOF-MS）was used for genetyping the 15 single nucleotide polymorphisms（SNP）of 6 microRNAs.3 Statistical analysis Mann-Whitney U,Jonckheere-Terpstra andχ² tests were used to assess the differences among the control and Coke oven emissions COEs groups with regard to continuous variables and categorical variables.A goodness-of-fitχ² analysis was used to test the Hardy–Weinberg equilibrium.Association analysis was performed by general linear models or,in which genotypes with three levels can be modeled as nominal variables without assuming additive models.False discovery rate（FDR）adjustment was used for multiple comparisons and FDR<0.05 was defined as the significance level.The relationships of SNPs and COEs exposure levels with T-AOC of plasma were tested by introducing the SNP* COEs exposure levels into the models.All the statistical analyzes were performed with IBM SPSS 21.0 statistics and the significance level was 0.05.Benchmark Dose Software（BMDS）Version 2.63（U.S.EPA）with BMDS Wizard（ICF international,version 1.1）was used to calculate BMD and its lower 95%confidence limit（BMDL）for risk assessment,with a 10%BMR level.Results1.The T-AOC and MDA of plasma in COEs exposed group were significantly lower than that in the control group（P<0.001）respectively and the CAT of plasma were significantly higher than that in the control group（P=0.042）.The T-AOC in plasma exhibited significant differences by gender,age,smoking status,alcohol consumption and BMI among the exposed group but no significant differences of CAT in plasma.The MDA exhibited significant differences by BMI and working years and H₂O₂ exhibited significant differences by BMI in in exposed group（P<0.05）.2.There were significant dose response relationships of cumulative exposure doses of COEs and with T-AOC,MDA and CAT（Ptrend<0.05）.There were significant negative dose response relationships of 1-hydroxypyrene and 3-hydroxyphenanthrene with T-AOC and MDA,but positive dose response relationships with CAT and H₂O₂（Ptrend<0.05）.BMD research showed that the BMDL of COEs was BMDL=1.465mg/（m³·year）for males and 0.752 mg/（m³·year）for females,corresponding the contact limits of COEs in the male and female were 0.042 mg/m³ and 0.021 mg/m³respectively,with the average working age of 35.3.miR-145 rs41291957 G were suggestively associated with T-AOC in coke oven workers with and without FDR adjustment（P=0.003,P=0.036）.The interactions of miR-145 rs41291957 and the cumulative exposure doses of COEs were associated with plasma T-AOC(P_interaction<0.05).Conclusions1.Statistically significant dose-response relationship between the cumulative exposure doses and T-AOC(P_trend<0.05)was found and the BMDL for males and females were 1.465 mg/（m3?year）and 0.752 mg/（m³·year）,corresponding the contact limits 0.042 mg/m³ and 0.021 mg/m³.It is suggested that the PC-TWA（0.1 mg/m³）of COEs in current occupational environment should be appropriately reduced2.miR-145 rs41291957 G were suggestively associated with T-AOC in coke oven workers.The interactions of miR-145 rs41291957 and the cumulative exposure doses of COEs were associated with plasma T-AOC.