| Objective:1.To explore the association between polycyclic aromatic hydrocarbons(PAHs)exposure and neurobehavioral function in coal miners and their possible dose-response relationships,and to further explore the relative weights of each PAHs metabolite in the association between mixed exposure and neurobehavioral function.2.To investigate the association of mitochondrial DNA copy number(mt DNAcn)with PAHs exposure and neurobehavioral function of coal miners and its dose-response relationship,and to further explore the possible role of mt DNAcn in the association between PAHs exposure and neurobehavioral function.Methods:In this study,we selected 637 coal miners as subjects,and collected their demographic information and biological samples for subsequent analysis.PAHs exposure level was determined by high-performance liquid chromatography,the neurobehavioral function was assessed by Neurobehavioral Core Test Battery,and mt DNAcn content was determined by real-time fluorescence quantitative PCR.Using SAS 9.4 and 4.1 R for data analysis,ANOVA,?~2 test and non-parametric test were used to compare the differences in distribution between the three groups.Spearman rank correlation was used to analyze the correlation between four kinds of PAHs metabolites.The generalized linear model was adopted to explore the correlation and linear trend between PAHs exposure,neurobehavioral function and mt DNAcn;Restricted Cubic Spline(RCS)was used to analyze the possible dose-response relationship.Weighted Quantile Sum(WQS)was used to analyze the correlation between PAHs mixed exposure and outcome,and the relative weight of the correlation.The software package"Mediation"was further used to analyze the possible mediating role of mt DNAcn in the association between PAHs exposure and neurobehavioral function.Results:1.Basic characteristics of the subjectsAccording to the quantile of PAHs exposure level,subjects were divided into low exposure group(n=212),medium exposure group(n=213)and high exposure group(n=212).There were statistically significant differences in education level,tea drinking,shift status and workplace among different exposure groups(P<0.05).2.The level of PAHs exposureAccording to the average level of exposure,we ranked the exposure of coal miners to four kinds of PAHs from low to high.The lowest is 1-PRY,followed by9-PHE,then 2-FLU,and finally is 2-NAP.There was a positive correlation among all metabolites,among which 9-PHE had the strongest correlation with 1-PYR(r correlation=0.40).3.The levels of neurobehavioral function and mt DNAcn in subjectsThe backward digit span,digital symbol and vision retention were statistically significant differences in different exposed groups(P<0.05).The neurobehavioral function score of the high exposure group was lower than that of low and medium exposure group.The mt DNAcn levels among the three groups were statistically significant difference(P<0.05),and the mt DNAcn of high exposure was significantly lower than low and medium exposure groups.4.Association between PAHs exposure and neurobehavioral functionIn the generalized linear model,after adjusting for age,working time,education level,working place,shift situation and so on,we found that 2-NAP was correlated with the backward digit span and digital symbol,2-FLU was correlated with the non-preferred hand,and 1-PYR and∑OH-PAHs were correlated with the digital symbol(P for trend<0.05).RCS analysis showed that there were dose-response relationships between the above associations(P for overall<0.05,P for nonlinear<0.05).In addition,there were also associations between 2-FLU and preferred hand,and 9-PHE and vigor-activity(P for trend<0.05),but no dose-response relationship was found in RCS analysis(P for nonlinear>0.05).The results of WQS regression showed that 2-NAP and 2-FLU were the main pollutants in the association between PAHs exposure and neurobehavioral function.5.Association between PAHs exposure and mt DNAcnAfter adjusting factors such as age,working time,education level,working place,shift situation and so on in the generalized linear model,we found that 2-NAP,2-FLU and∑OH-PAHs were negatively correlated with mt DNAcn.The results of RCS analysis showed that there was a dose-response relationship between 2-FLU and total OH-PAHs and mt DNAcn.The dose-response relationship between 2-FLU and mt DNAcn was approximately"J"shape(P for overall<0.05,P for nonlinear<0.05).WQS regression showed that 1-PYR was the main pollutant in the association between PAHs exposure and mt DNAcn.6.Association between mt DNAcn and neurobehavioral functionAfter adjusting for age,working time,education level,working place,shift situation and so on,we observed that mt DNAcn was correlated with mean reaction time and digital symbol in the generalized linear model(P for trend<0.05).RCS analysis showed that there was a dose-response relationship between mt DNAcn and the mean reaction time(P for overall<0.05,P for nonlinear<0.05).7.Mediating effect of mt DNAcn in the association between PAHs exposure and neurobehavioral functionIn the mediating effect model,we adjusted the confounding factors such as age,working time,education level,working place,shift situation and other OH-PAHs,and took PAHs metabolites as independent variables,mt DNAcn as mediating variables,and neurobehavioral function(digital symbol)as dependent variables.We didn’t find the mediating effect of mt DNAcn in the association between PAHs exposure and neurobehavioral function.Conclusions:1.PAHs exposure level of coal miners was higher than that of the general population,and there was a dose-response relationship between PAHs exposure and neurobehavioral function.With the increase in exposure level,neurobehavioral function decreased.2-NAP and 2-FLU play the major role in the association between PAHs exposure and neurobehavioral function.2.PAHs exposure has a negative dose-response relationship with mt DNAcn in coal miners,and with the increase of exposure level,mt DNAcn decreased.1-PYR played a major role in the association between PAHs exposure and mt DNAcn.The level of mt DNAcn is related to neurobehavioral function.No mediating effect of mt DNAcn was found in the association between PAHs exposure and neurobehavioral function. |
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