砷暴露工人CYTB基因DNA损伤与甲基化、基因多态性的相关性研究  

Study on the correlation between the DNA damage level of Cytb gene and the arsenic methylation degree,gene polymorphism in arsenic-exposed workers

作　　者：李舒婷 陈斌 段婷芝 杨雪飞 杨欣达 杨净超 徐婕 LI Shu-ting;CHEN Bin;DUAN Ting-zhi;YANG Xue-fei;YANG Xin-da;YANG Jing-chao;XU Jie(Yunnan Provincial Key Laboratory of Public Health and Biosafety&School of Public Health,Kunming Medical University,Kunming,Yunnan 650500,China;不详)

机构地区：[1]云南省公共卫生与生物安全重点实验室&昆明医科大学公共卫生学院,云南昆明650500 [2]云南省教育厅公共卫生与疾病防控重点实验室&昆明医科大学公共卫生学院

出　　处：《现代预防医学》2025年第4期616-621,628,共7页Modern Preventive Medicine

基　　金：国家自然科学基金(82160607);昆明医科大学环境与职业砷暴露致癌研究科技创新团队(CXTD202201);云南省教育厅公共卫生与疾病防控重点实验室(2023YB03)。

摘　　要：目的研究砷暴露工人CYTB基因的DNA损伤水平与甲基化程度、FEN1、XPC基因的多态性之间的相关性。方法选取云南省南部山区某焦炉厂存在职业性砷暴露的79名工人作为暴露组,与之同村的24名农业工人作为对照组,采集研究对象的尿液和外周血,检测尿液中砷及其代谢产物的浓度、百分比,检测外周血中CYTB基因的DNA损伤水平。结果暴露组尿液中的无机砷(iAs)、单甲基砷酸(MMA)、二甲基砷酸(DMA)的浓度均高于对照组(P均<0.01)。甲基化水平上,暴露组MMA%、一级甲基化指数(PMI)显著高于对照组,DMA%、二级甲基化指数(SMI)显著低于对照组(P均<0.01)。线性回归结果显示CYTB基因的DNA损伤水平与MMA%呈正相关(P<0.01),与SMI呈负相关(P<0.001)。FEN1基因rs174538位点基因型为AA或GA+AA的受试者的CYTB基因DNA损伤水平显著高于该位点基因型为GG的受试者(P<0.05),但XPC的基因型与CYTB基因的DNA损伤水平无统计学相关性(P>0.05)。结论焦炉厂工人的职业性砷暴露会导致尿中砷及其代谢产物的浓度增加、体内砷代谢的甲基化程度降低,CYTB基因的DNA损伤可以作为指示体内甲基化水平的受损、早期健康损害的标志物,并且,FEN1基因rs174538位点的突变可以作为砷暴露人群疾病易感性的指标。Objective To investigate the correlation between the DNA damage level of the CYTB gene and the arsenic methylation level,FEN1 and XPC gene polymorphism in workers exposed to arsenic.Methods A total of 79 workers exposed to occupational arsenic in a coke oven factory in the southern mountainous area of Yunnan Province were selected as the exposure group,and 24 agricultural workers from the same village were selected as the control group.The urine and peripheral blood samples of the subjects were collected.The concentration and percentage of arsenic and its metabolites were detected in the urine,and the DNA damage level of the CYTB gene was detected in peripheral blood.Results The concentrations of inorganic arsenic(iAs),monomethylarsonic acid(MMA),and dimethylarsonic acid(DMA)in the urine of the exposure group were higher than those of the control group(P<0.01).The methylation level of the exposure group was significantly higher than that of the control group in terms of MMA%and primary methylation index(PMI),while the DMA%and secondary methylation index(SMI)were significantly lower than those of the control group(P<0.01).Linear regression analysis showed that the DNA damage level of the CYTB gene was positively correlated with MMA%(P<0.01)and negatively correlated with SMI(P<0.001).The subjects with genotypes AA or GA+AA at the rs174538 locus of the FEN1 gene had significantly higher DNA damage levels of the CYTB gene than those with genotypes GG at this locus(P<0.05).However,there was no statistical correlation between the genotype of XPC and the level of DNA damage in the CYTB gene(P>0.05).Conclusion Occupational arsenic exposure can lead to increased concentrations of arsenic and its metabolites in urine and decreased methylation of arsenic metabolism in the body.The DNA damage of the CYTB gene can be used as a marker of damage and early health damage in the body,and the mutation at the rs174538 locus of the FEN1 gene is associated with DNA damage of the CYTB gene,which can be used as an indicator of disease s

关 键 词：职业性砷暴露 CYTB基因 DNA损伤水平 FEN1基因 

分 类 号：R135.1[医药卫生—劳动卫生] R-33[医药卫生—公共卫生与预防医学]