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Effect Of LncRNA Gene Polymorphisms On Coke Oven Workers’ Mitochondrial DNA Copy Number

Posted on:2022-08-18Degree:MasterType:Thesis
Country:ChinaCandidate:X L LiFull Text:PDF
GTID:2504306605955819Subject:Master of Public Health
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Research ObjectiveThis study aims to investigate the relationship between the SNPs of three lncRNAs(ANRIL,P53RRA,and MEG3)and mtDNAcn of coke oven workers’ peripheral blood leukocytes.Further to explore the interaction effect of lncRNA SNPs and polycyclic aromatic hydrocarbons(PAHs)exposure on coke oven workers’ mtDNAcn.That would provide a theoretical basis for screening and protection of susceptible population exposed to occupational PAHs.Methods1 SubjectsA total of 544 coke oven workers aged between 18 and 60 who had worked in a coking plant in Anyang for more than one year were selected as the exposure group.In the same period,238 public institution workers who had no exposure to occupational toxic or harmful substances served as the control group.After informed consent of the study subj ects,demographic epidemiological data were collected using questionnaires,and peripheral blood and urine biological samples were collected.2 Research methodsHigh-performance liquid chromatography was used to detect the concentrations of 1-hydroxypyrene(1-OHPYR),1-hy droxynathalene(1-OHNAP),2hydroxynathalene(2-OHNAP),and 3-hydroxyphenanthrene(3-OHPHE)in urine.The genomic DNA of peripheral white blood cells was extracted from the study subjects using the medium volume whole blood genome extraction kit.The mtDNAcn of peripheral blood leukocytes was determined by real-time fluorescent quantitative polymerase chain reaction,and the matrix-assisted laser desorption ionization time-offlight mass spectrometry was used to genotyping the Twenty-two polymorphisms of ANRIL,P53RRA,and MEG3.3 Statistical analysisEpidata 3.0 was used to enter the questionnaire information.SPSS 27.0 statistical software was used to analyze data.The data of four urinary PAHs metabolites were converted by natural logarithm to satisfy normal distribution.The independent sample t test was used to analyze the difference of continuous variables in demographic data and urinary PAHs metabolites between the exposure group and the control group.Theχ2 test was used to analyze the distribution of the study objects in general classification variables and ANRIL,P53RRA,and MEG3 genetic polymorphisms both in the exposure group and the control group.Covariance analysis was used to explore the influence of the demographic data and the ANRIL,P53RRA,and MEG3 genetic SNPs on the coke oven workers’ mtDNAcn.The generalized linear model was used to analyze the interaction effect of SNPs and PAHs on mtDNAcn.The test level α=0.05.Results1.The concentrations of four urinary PAHs metabolites in the exposure group were significantly higher than those in the control group(P<0.05).The mtDNAcn of peripheral blood leukocytes in PAHs exposure group(0.60±0.29)was significantly lower than that in the control group(1.03±0.31)(t=18.931,P<0.001).2.The univariate covariance analysis showed that the coke oven workers harboring MEG3 rs11859 TT genotype(0.53±0.29)had significantly lower mtDNAcn than GT+GG genotype(0.62±0.29)(P=0.004)in the exposure group,andthe coke oven workers harboring MEG3 rs3742396 GG genotype(0.55±0.28)had significantly lower mtDNAcn than AG genotype(0.62±0.29)(P=0.034)in the exposure group.Multivariate covariance analysis showed that the influencing factors of decreased mtDNAcn included PAHs exposure[β(95%CI)=-0.430(-0.477,-0.384),P<0.001]and MEG3 rs11859 TT genotype MEG3 rs11859 TT[β(95%CI)=-0.078(-0.130,0.026),P=0.004].3.Generalized linear model was used to analyze the effect of gene-environment interaction on the mtDNAcn of coke oven workers.The results showed that there is a interaction effect MEG3 rs11627993(AA genotype)× PAHs[β(95%CI)=0.097(0.004,0.190),P=0.040]and MEG3 rs2400942(GA+AA genotype)× PAHs[β(95%CI)=0.141(0.018,0.263),P=0.024]on coke oven workers’ mtDNAcn.Conclusions1.PAHs exposure and MEG3 rs11859 TT genotype may be risk factors for the mtDNAcn in the coke oven workers.2.There is an interaction effect MEG3 rs11627993(AA genotype)with PAHs,and MEG3 rs2400942(GA+AA genotype)with PAHs on coke oven workers’mtDNAcn.
Keywords/Search Tags:Polycyclic aromatic hydrocarbons, Long noncoding RNA, MEG3 rs11859, Single nucleotide polymorphism, Mitochondrial DNA copy number, coke oven worker
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