High pesticide exposure events and DNA methylation among pesticide applicators in the agricultural health study.
High pesticide exposure events and DNA methylation among pesticide applicators in the agricultural health study.
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DOI：
10.1002/em.22067
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发表时间：
2017-01
影响因子：
2.8
通讯作者：
Baccarelli A
中科院分区：
文献类型：
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作者：
Rusiecki JA;Beane Freeman LE;Bonner MR;Alexander M;Chen L;Andreotti G;Barry KH;Moore LE;Byun HM;Kamel F;Alavanja M;Hoppin JA;Baccarelli A
接触农药与急性和慢性不良健康影响有关。DNA甲基化（DNAm）可能介导这些效应。我们在农业健康研究（AHS）中评估了农药施用者经历异常高农药暴露事件（HPEE）与DNA m之间的关联，AHS是一项对爱荷华州和北卡罗来纳州农药施用者的前瞻性研究。从男性AHS农药施用者（n=695）的全血中提取DNA。问卷调查数据用于确定参与者一生中HPEE的发生率。焦磷酸测序用于定量CDH 1、GSTp 1和MGMT启动子以及重复元件LINE-1中的DNAm。线性和稳健回归分析评估了HPEE和DNAm之间的调整关联。曾经患有HPEE（n=142; 24%）与GSTp 1启动子CpG 7（chr 11：67，351，134; p<0.01）和CpG间平均值（chr 11：67，351，099，67，351，124 -145; p<0.01）的DNAm升高相关。在分层分析中，与HPEE相关的GSTP 1启动子DNAm升高在>59岁和血浆叶酸水平≤16.56 ng/mL的施用者中更为明显（p-相互作用<0.01）; HPEE与MGMT启动子DNAm在CpG 2（chr10：131，265，803; p=0.03），CpG3（chr 10：131，265，810; p=0.05），CpG间的平均值（chr 10：131，265，796 -810; p=0.03），血浆叶酸≤16.56 ng/mL的施用者LINE-1 DNAm降低（p=0.05）。非特异性HPEE可能导致GSTp 1中DNA m增加，在某些组中，MGMT和LINE-1中DNA m减少。这些改变对疾病发展的影响尚不清楚，但GSTp 1启动子DNAm升高和随后的基因失活一直与前列腺癌相关。
Pesticide exposure has been associated with acute and chronic adverse health effects. DNA methylation (DNAm) may mediate these effects. We evaluated the association between experiencing unusually high pesticide exposure events (HPEEs) and DNAm among pesticide applicators in the Agricultural Health Study (AHS), a prospective study of applicators from Iowa and North Carolina. DNA was extracted from whole blood from male AHS pesticide applicators (n=695). Questionnaire data were used to ascertain the occurrence of HPEEs over the participant's lifetime. Pyrosequencing was used to quantify DNAm in CDH1, GSTp1, and MGMT promoters, and in the repetitive element, LINE-1. Linear and robust regression analyses evaluated adjusted associations between HPEE and DNAm. Ever having an HPEE (n=142; 24%) was associated with elevated DNAm in the GSTp1 promoter at CpG7 (chr11:67,351,134; p<0.01) and for the mean across CpGs (chr11:67,351,099, 67,351,124-145; p<0.01). In stratified analyses, elevated GSTP1 promoter DNAm associated with HPEE was more pronounced among applicators >59 years and those with plasma folate levels ≤16.56 ng/mL (p-interaction <0.01); HPEE was associated with reduced MGMT promoter DNAm at CpG2 (chr10:131,265,803; p=0.03), CpG3 (chr10:131,265,810; p=0.05), and the mean across CpGs (chr10:131,265,796-810; p=0.03) among applicators >59 years and reduced LINE-1 DNAm (p=0.05) among applicators with ≤16.56 ng/mL plasma folate. Non-specific HPEEs may contribute to increased DNAm in GSTp1, and in some groups, reduced DNAm in MGMT and LINE-1. The impacts of these alterations on disease development are unclear, but elevated GSTp1 promoter DNAm and subsequent gene inactivation has been consistently associated with prostate cancer.