慢性砷暴露对CDH1、GSTP 1、MGMT、EREG和 ERCC 2基因启动子区甲基化的影响

目的探讨慢性砷暴露对CDH1、GSTP 1、MGMT、EREG和ERCC 2基因启动子区甲基化的影响以及无机砷对人体的远期毒性作用。方法采用病例对照研究方法,利用MethylTargetTM甲基化检测技术对病例组、暴露组、改水组、对照组CDH1、GSTP 1、MGMT、EREG和ERCC 2基因启动子区CpG岛甲基化水平进行检测。结果病例组与对照组比较,GSTP 1、MGMT和ERCC 2基因CpG位点甲基化差异显著;ERCC 2基因甲基化单倍型ttttttccccctcc、ttttttccctctcc和ttttttccccctct甲基化差异显著。暴露组与对照组比较,CDH1、GSTP 1、MGMT和ERCC 2基因CpG位点甲基化差异显著;CDH1基因甲基化单倍型tttttttttttctttttttttt、MGMT基因甲基化单倍型cttttttttttttttttttttt和cccccccttttttttttttttt以及ERCC 2基因甲基化单倍型ttttttccccctcc甲基化差异显著;MGMT和ERCC 2基因启动子区整体甲基化水平显著高于对照组。改水组与对照组比较,GSTP 1、MGMT、EREG和ERCC 2基因CpG位点甲基化差异显著;GSTP 1基因甲基化单倍型ttttttttttttttttttttttttttttttt、EREG基因甲基化单倍型ccccctctcccccccc以及ERCC 2基因甲基化单倍型ttttttttttttcttttt和tttttttttttttttttt甲基化差异显著;MGMT基因启动子区整体甲基化水平仍显著高于对照组。结论 CDH1、GSTP 1、MGMT和ERCC 2基因在无机砷暴露条件下可能发生异常甲基化;GSTP1、MGMT和ERCC 2基因启动子区发生甲基化可能参与了地砷病的发生发展过程;改水后MGMT基因甲基化仍然表现为异常,无机砷对人体具有长期的毒性作用。

The effects on CDH1,GSTP 1,MGMT,EREG and ERCC 2 gene promoter methylation exposed to chronic arsenic

Objective To investigate the effects of chronic arsenic exposure on methylation of CDH1,GSTP1,MGMT,EREG,and ERCC2 gene promoters and the long-term toxic effects of inorganic arsenic on humans.Methods MethylTargetTM methylation detection technology was employed to analyze promoter methylation of CDH1,GSTP 1,MGMT,EREG and ERCC 2 genes in the cases group,exposure group,the improvement of water group and the control group.Results Case group compared with control group,there was a significant difference in the methylation of the GSTP 1,MGMT and ERCC 2 gene CpG loci;methylation haplotypes ttttttccccctcc,ttttttccctctcc and ttttttccccctct methylation of the ERCC 2 gene were significantly different.Exposed group compared with control group,methylation of CpG sites in CDH1,GSTP1,MGMT,and ERCC2 genes was significantly different;CDH1 gene methylation haplotype tttttttttttctttttttttttt,MGMT gene methylation haplotype cttttttttttttttttttttttttt and cccccccttttttttttttttttttt and ERCC 2 gene methylation haplotype ttttttccccctcc methylation were significantly different;The methylation level of the MGMT and ERCC 2 gene promoter regions was significantly higher than that of the control group.Compared with the control group,there were significant differences in methylation of CpG sites of GSTP 1,MGMT,EREG and ERCC 2 genes;GSTP 1 gene methylation haplotype ttttttttttttttttttttttttttttttttttttttt,EREG gene methylation haplotypes ccccctctcccccccc and ERCC 2 gene methylation haplotypes ttttttttttttcttttt and tttttttttttttttttttt methylation were significantly different;the methylation level of MGMT gene promoter region was still significantly higher than that of the control group.Conclusion Abnormal methylation of CDH1,GSTP1,MGMT and ERCC2 genes may occur under inorganic arsenic exposure conditions;methylation of GSTP1,MGMT and ERCC2 gene promoter regions may be involved in the occurrence and development of arsenic disease;After the methylation of the MGMT gene is still abnormal,inorganic arsenic has long-term toxic effects on the human body.