| ObjectiveLead(Pb)is a common heavy metal element widely distributed in the environment.Lead is widely used in smelting,chemical industry,lead battery manufacturing and other industries because of its low melting point,easy access and corrosion resistance.With the rapid development of lead industry in China,occupational chronic lead poisoning has become a major problem in the field of occupational disease prevention.The study will understand the lead exposure of lead-acid battery enterprises and make clear the harm degree of lead exposure.To explore the associations among different blood lead levels under the same external exposure conditions microRNA expression levels and single nucleotide polymorphisms of mature related genes.It provides basis for prevention and control of occupational lead hazards.Methods1.Investigation on classification of lead concentration hazard in lead-acid battery enterprisesTo detect the lead concentration of all lead-related positions in a lead-acid battery enterprise.The results were classified according to relevant standards.Identify key protection and management positions.2.The association between differential expression of microRNA and blood lead level in lead-related workers under the same exposure conditionsThe lead related workers of posts with the same or similar external exposure conditions in several lead-acid battery enterprises were chosen as the research subjects,and both high blood lead group and low blood lead group were selected among them.among which 10%lead workers with relatively low blood lead concentration were selected as the low-lead group,and another 10%lead workers with relatively high blood lead concentration were classified as the high-lead group.The difference of microRNAs expression profiles between these two groups was detected by gene chip technology,and the results were verified by PCR technology to clarify the associations between abnormal expression of microRNAs and blood lead concentration.On this basis,these microRNAs were analyzed by bioinformatics,and their possible downstream genes and corresponding signaling pathways were preliminarily explored.3.The association between different blood lead levels and single nucleotide polymorphisms of microRNA maturation-related genes under the same exposure conditionsBased on the literature analysis,five essential genes related to microRNA maturation were selected,i.e.DROSHA?DICER?XP05?RAN and GEMIN4.According to NCBI SNP and 1000 Genomes databases,SNP sites with MAF>0.05 and the minimum gene frequency carrying populations greater than 10 were screened out using Haploview4.2 software.Genotyping was carried out in high and low lead groups,to explore the association between SNPs of microRNA maturation related genes and blood lead level by logistic regression.Results1.Investigation on classification of lead concentration hazard in lead-acid battery enterprisesIn all lead related jobs,the lead concentration in the posts of casting,mixing,disc grinding,packing and brushing,welding,and bushing were found to exceed the national standard.Casting and bushing were working posts with mild hazard,while mixing,packing and brushing,welding,and disc grinding were the posts with moderate hazards.The rest of the above-mentioned jobs are relatively harmless.2.The association between differential expression of microRNA and blood lead level in lead-related workers under the same exposure conditionsThe gene chip showed that the expression levels of 16 microRNAs in the high-lead group were different from those in the low-lead group.Among them,the fold change of microrna-520,microrna-211,microrna-148 and microrna-141 were 5.41,3.46,2.52 and 2.17.The fold change of microrna-572 and microrna-130b were 0.39 and 0.45 respectively.The results of PCR validation showed that there were significant differences among microRNA-520,microRNA-211,microRNA-148 and microRNA-572(P<0.05).Bioinformatics analysis revealed that microRNA-520,microRNA-211 and microRNA-148 may be related to SUMO pathway,Bcl-2 pathway and endoplasmic reticulum stress pathway respectively.MicroRNA-572 does not match any of the important signaling pathways..3.The association between different blood lead levels with single nucleotide polymorphisms of microRNA maturation-related genes under the same exposure conditionsAmong microRNA maturation related genes,.only XP05 gene rs2257082 genotype was found to be statistically different between high lead group and low lead group(P<0.05),OR(95%%)was 1.63(1.07?2.47)P=0.022,the risk of high blood lead in workers exposed to CC genotype is 2.6 times higher than that of TT genotype,OR(95%%)was 2.6(1.08?6.28)P=0.034.Conclusions1.In this lead-acid battery enterprise,posts with excessive lead are mixing,grinding disc,packing and brushing,welding,and bushing positions,which needs to be treated with emphasis.2.The expression levels of microRNA-520,microRNA-211 and microRNA-148 in workers with high blood lead level and low blood lead level under the same external exposure conditions were significantly different.They can be further studied as diagnostic markers of lead exposure.3.The C allele of XPO5 SNP rs2257082 is a risk factor for lead exposure,which can provide evidence for pre-job screening of lead-related workers.. |
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