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北卡罗来纳州农场工人和非农场工人在生长季节期间的DNA甲基化变化存在差异。

Changes in DNA methylation over the growing season differ between North Carolina farmworkers and non-farmworkers.

作者信息

Howard Timothy D, Hsu Fang-Chi, Chen Haiying, Quandt Sara A, Talton Jennifer W, Summers Phillip, Arcury Thomas A

机构信息

Center for Genomics and Personalized Medicine Research, Wake Forest School of Medicine, Medical Center Blvd, Winston-Salem, NC, 27157, USA.

Department of Biostatistical Sciences, Division of Public Health Sciences, Wake Forest School of Medicine, Medical Center Blvd, Winston-Salem, NC, 27157, USA.

出版信息

Int Arch Occup Environ Health. 2016 Oct;89(7):1103-10. doi: 10.1007/s00420-016-1148-0. Epub 2016 Jun 27.

Abstract

PURPOSE

The occupational risk to farmworkers, particularly chronic exposure to pesticides, is an acknowledged environmental and work-related health problem. Epigenetics has recently been shown to contribute to a number of complex diseases and traits, including measures of cognitive function and preclinical neurodegenerative disease. We sought to determine whether changes in DNA methylation existed between farmworker and non-farmworker populations and to identify the genes most likely involved in those changes.

METHODS

Eighty-three farmworkers and 60 non-farmworkers were selected from PACE4, a community-based, participatory research project comparing occupational exposures between immigrant Latino farmworker and non-farmworker manual workers. Measurements of DNA methylation were performed with the Infinium HumanMethylation450 BeadChip, at the beginning and end of the 2012 growing season. Bonferroni adjustment was used to identify significant findings (p = 1.03 × 10(-7), based on 485,000 tested methylation sites), although less stringent criteria (i.e., p ≤ 1 × 10(-6)) were used to identify sites of interest. Expression quantitative trait locus (eQTL) databases were used to help identify the most likely functional genes for each associated methylation site.

RESULTS

Methylation at 36 CpG sites, located in or near 72 genes, differed between the two groups (p ≤ 1 × 10(-6)). The difference between the two groups was generally due to an increase in methylation in the farmworkers and a slight decrease in methylation in the non-farmworkers. Enrichment was observed in several biological pathways, including those involved in the immune response, as well as growth hormone signaling, role of BRCA1 in DNA damage response, p70S6K signaling, and PI3K signaling in B lymphocytes.

CONCLUSIONS

We identified considerable changes in DNA methylation at 36 CpG sites over the growing season that differed between farmworkers and non-farmworkers. Dominant pathways included immune-related (HLA) processes, as well as a number of diverse biological systems. Further studies are necessary to determine which exposures or behaviors are responsible for the observed changes, and whether these changes eventually lead to disease-related phenotypes in this population.

摘要

目的

农场工人面临的职业风险,尤其是长期接触农药,是一个公认的环境和职业相关健康问题。近期研究表明,表观遗传学与许多复杂疾病和性状有关,包括认知功能指标和临床前神经退行性疾病。我们试图确定农场工人和非农场工人群体之间DNA甲基化是否存在差异,并找出最有可能参与这些变化的基因。

方法

从PACE4项目中选取了83名农场工人和60名非农场工人,该项目是一项基于社区的参与性研究项目,比较移民拉丁裔农场工人和非农场工人体力劳动者之间的职业暴露情况。在2012年生长季节开始和结束时,使用Infinium HumanMethylation450 BeadChip进行DNA甲基化测量。采用Bonferroni校正来确定显著结果(基于485,000个测试的甲基化位点,p = 1.03 × 10(-7)),不过使用了不太严格的标准(即p≤1×10(-6))来确定感兴趣的位点。利用表达数量性状位点(eQTL)数据库来帮助确定每个相关甲基化位点最可能的功能基因。

结果

两组之间位于72个基因内部或附近的36个CpG位点的甲基化存在差异(p≤1×10(-6))。两组之间的差异通常是由于农场工人甲基化增加,而非农场工人甲基化略有下降。在几个生物途径中观察到富集现象,包括参与免疫反应的途径,以及生长激素信号传导、BRCA1在DNA损伤反应中的作用、p70S6K信号传导和B淋巴细胞中的PI3K信号传导。

结论

我们发现在生长季节,农场工人和非农场工人之间36个CpG位点的DNA甲基化存在显著变化。主要途径包括免疫相关(HLA)过程,以及许多不同的生物系统。需要进一步研究以确定哪些暴露或行为导致了观察到的变化,以及这些变化是否最终导致该人群中与疾病相关的表型。

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