Methylation alterations at imprinted genes detected among long-term shiftworkers.

Methylation alterations at imprinted genes detected among long-term shiftworkers.
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DOI:
10.1002/em.21752
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发表时间:
2013-03
影响因子:
2.8
通讯作者:
Zhu Y
Zhu Y
中科院分区:
环境科学与生态学3区
文献类型:
--
作者:
Jacobs DI;Hansen J;Fu A;Stevens RG;Tjonneland A;Vogel UB;Zheng T;Zhu Y

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通过轮班工作在夜间暴露于光线与DNA甲基化的改变和癌症发展的风险增加有关。使用Illumina Infinium甲基化分析,我们分析了56个正常印迹基因的启动子区域中397个CpG位点的甲基化水平,以研究轮班工作是否与甲基化模式的改变相关。与10名年龄和叶酸摄入量相匹配的日工相比,10名长期轮班的女性在20个CpG位点的甲基化显著较高,在30个CpG位点的甲基化显著较低(P < 0.05)。基于多个CpG位点的甲基化变化幅度和变化方向的一致性,在DLX5、IGF2AS和TP73中观察到轮班工人甲基化模式改变的最强有力证据,并且使用定量DNA甲基化分析观察到一致的结果。我们的结论是,长期轮班工作可能会改变甲基化模式的印记基因,这可能是一个重要的机制,轮班工作具有致癌潜力,值得进一步调查。
Exposure to light at night through shiftwork has been linked to alterations in DNA methylation and increased risk of cancer development. Using an Illumina Infinium Methylation Assay, we analyzed methylation levels of 397 CpG sites in the promoter regions of 56 normally imprinted genes to investigate whether shiftwork is associated with alteration of methylation patterns. Methylation was significantly higher at 20 CpG sites and significantly lower at 30 CpG sites (P < 0.05) in 10 female long-term shiftworkers as compared to 10 female age- and folate intake-matched day workers. The strongest evidence for altered methylation patterns in shiftworkers was observed for DLX5, IGF2AS, and TP73 based on the magnitude of methylation change and consistency in the direction of change across multiple CpG sites, and consistent results were observed using quantitative DNA methylation analysis. We conclude that long-term shiftwork may alter methylation patterns at imprinted genes, which may be an important mechanism by which shiftwork has carcinogenic potential and warrants further investigation.