Influences Of MiRNAs Polymorphism And Coke Oven Emissions Exposure On Telomere Length Of Coke Oven Workers

ObjectiveExposure to coke oven emissions(COEs)could shorten telomere length of the peripheral blood leukocytes of coke oven workers,and the shortened telomere length of coke oven workers may be related to genetic polymorphisms such as metabolic enzymes,DNA damage repair and cell cycle.However,the relationships between a large number of miRNAs gene polymorphisms and telomere shortening are unclear.Therefore,the study is aimed to explore occupational exposure limits of COEs by analyzing the dose-response relationship between COEs exposure and telomere shortening and benchmark dose,and screened susceptible genotypes by analyzing the relationship between 15 miRNAs gene polymorphisms and telomere length.Methods and Materials1 SubjectsThe COEs exposure group was composed of 544 coke oven workers recruited from a coking plant;the control group was composed of 238 people from the same area with the normal health examination,no a history of exposure to COEs and other poisons.The questionnaire investigated the subject information,such as name,sex,date of birth,smoking,drinking and professional history.2 MethodsCOEs concentrations in air and cumulative exposure doses of subjects were detected and estimated.The relative telomere length in peripheral blood leukocytes was measured by qPCR methods.The method based on Matrix assisted laser desorption ionization time of flight mass spectrometry was applied to detect genotype of 15 single nucleotide polymorphism in 8 miRNAs.The U.S.Environmental Protection Agency benchmark dose software(BMDs)and Bayesian benchmark dose estimation(BBMD)system to calculate benchmark dose(BMD)and benchmark dose lower bound(BMDL)of telomere shortening induced by COEs exposure.3 Statistical analysisSPSS21.0 statistics software was applied to data analysis.Telomere length was normal distribution for subsequent analysis after logarithmic transformation.The covariance analysis was conducted to explore the influence of miRNAs SNPs on telomere length after adjusted for sex,age,smoking,drinking,BMI,and the cumulative exposure.The generalized linear model was applied to investigate the relationship between the interaction of miRNAs and COEs exposure and telomere length.The significance level was taking as 0.05.Results1.The telomere length of coke oven workers was shorter than that of controls(4.56±0.84 vs.4.99±0.75,t=3.23,P<0.05).The telomere length decreased with the increase of cumulative exposure dose(P<0.05),and there was a dose-response relationship between them.Further,the BMD inducing telomere damage was estimated,and the BMDL of the total population obtained from BMDs and BBMD were 2.04mg/m~3·year and 2.24 mg/m~3·year.Dividing a total working life 40 years into the BMDLs,the occupational exposure limit of COEs were 0.051 mg/m~3 and 0.056 mg/m~3,respectively.2.After adjusting for factors such as gender and age,in the exposure group,the covariance results showed that the susceptibility gene locus for shortened telomere length in the exposed group include miR-612 rs1144925(TT/CC+CT,5.02±0.96 vs.4.54±0.83),miR-34A rs12128240(TT/CC+CT,4.18±0.74 vs.4.58±0.84),and miR-181B1rs12039395(GG+GT/TT,4.55±0.84 vs.4.80±0.81).Further,the generalized linear analysis showed that the mainly affected factors of shortening of telomere length of coke oven workers included miR-612 rs1144925(CT+TT)[β(95CI):-0.364(-0.627,-0.102),P=0.007],COEs exposure[β(95CI):-0.433(-0.564,-0.303),P<0.001],miR-181B1 rs12039395(GG+GT)[β(95CI):-0.290(-0.684,0.103),P=0.148],and COEs exposure×rs12039395(GG+GT)[β(95CI):0.546(0.089,1.003),P=0.019].Conclusions1.The occupational exposure reference limit for COEs obtained from this study was about 0.05 mg/m~3,which is lower than the current occupational exposure standard of 0.10 mg/m~3 for COEs in China,suggesting that more stringent occupational exposure limits for COEs need to be established to protect the health of coke oven workers.2.The main susceptibility factors for telomere length shortening in coke oven workers included COEs exposure,miR-612rs1144925 locus(CT+TT)genotype and miR-181B1rs12039395(GG+GT),and there was an interaction between rs12039395locus risk genotype and COEs exposure in telomere length shorting of coke oven workers.