近几十年来,农药在农业中的使用急剧增加。这导致这些物质广泛分散在环境中,污染暴露的工人和居住在农业地区附近的社区,并通过受污染的食品。除了急性中毒,长期接触农药会导致分子变化,这些变化正在变得更好理解。因此,这项研究的目的是评估,通过对文献的系统回顾,什么表观遗传改变与农药暴露有关。我们进行了系统评价和荟萃分析,包括病例对照,队列和横断面观察性流行病学研究,以验证表观遗传变化,比如DNA甲基化,组蛋白修饰和差异microRNA表达,暴露于任何类型杀虫剂的人类。收集了2005年至2020年之间发表的文章。两名不同的审阅者使用RayyanQCRI软件对研究进行了盲选择。完成后,对所选文章的数据进行提取和分析。28篇文章中的大多数包括评估全球DNA甲基化水平,最常报道的应对农药暴露的表观遗传修饰是全球DNA低甲基化。Meta分析显示Alu甲基化水平与β-六氯环己烷呈显著负相关,p,p-二氯二苯基二氯乙烷和p,对二氯二苯基乙烯水平。此外,据报道,一些特定基因在启动子区域高度甲基化,如CDKN2AIGF2,WRAP53α和CDH1,而CDKN2B和H19由于农药暴露而低甲基化。microRNAs的表达也随着杀虫剂的反应而改变,作为miR-223,miR-518d-3p,miR-597、miR-517b和miR-133b与许多人类疾病相关。因此,这项研究提供了证据,表明农药暴露可能导致表观遗传修饰,可能会改变全球和基因特异性的甲基化水平,全表观基因组甲基化和microRNA差异表达。
In recent decades, the use of pesticides in agriculture has increased dramatically. This has resulted in these substances being widely dispersed in the environment, contaminating both exposed workers and communities living near agricultural areas and via contaminated foodstuffs. In addition to acute poisoning, chronic exposure to pesticides can lead to molecular changes that are becoming better understood. Therefore, the aim of this study was to assess, through a systematic
review of the literature, what
epigenetic alterations are associated with pesticide exposure. We performed a systematic
review and meta-analysis including case-control, cohort and cross-sectional observational epidemiological studies to verify the
epigenetic changes, such as DNA methylation, histone modification and differential microRNA expression, in humans who had been exposed to any type of pesticide. Articles published between the years 2005 and 2020 were collected. Two different reviewers performed a blind selection of the studies using the Rayyan QCRI software. Post-completion, the data of selected articles were extracted and analyzed. Most of the 28 articles included evaluated global DNA methylation levels, and the most commonly reported
epigenetic modification in response to pesticide exposure was global DNA hypomethylation. Meta-analysis revealed a significant negative correlation between Alu methylation levels and β-hexachlorocyclohexane, p,p\'-dichlorodiphenyldichloroethane and p,p\'-dichlorodiphenylethylene levels. In addition, some specific genes were reported to be hypermethylated in promoter regions, such as CDKN2AIGF2, WRAP53α and CDH1, while CDKN2B and H19 were hypomethylated due to pesticide exposure. The expression of microRNAs was also altered in response to pesticides, as miR-223, miR-518d-3p, miR-597, miR-517b and miR-133b that are associated with many human diseases. Therefore, this study provides evidence that pesticide exposure could lead to
epigenetic modifications, possibly altering global and gene-specific methylation levels, epigenome-wide methylation and microRNA differential expression.