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Occupational exposure to pesticides is associated with differential DNA methylation.


ABSTRACT: OBJECTIVES:Occupational pesticide exposure is associated with a wide range of diseases, including lung diseases, but it is largely unknown how pesticides influence airway disease pathogenesis. A potential mechanism might be through epigenetic mechanisms, like DNA methylation. Therefore, we assessed associations between occupational exposure to pesticides and genome-wide DNA methylation sites. METHODS:1561 subjects of LifeLines were included with either no (n=1392), low (n=108) or high (n=61) exposure to any type of pesticides (estimated based on current or last held job). Blood DNA methylation levels were measured using Illumina 450K arrays. Associations between pesticide exposure and 420?938 methylation sites (CpGs) were assessed using robust linear regression adjusted for appropriate confounders. In addition, we performed genome-wide stratified and interaction analyses by gender, smoking and airway obstruction status, and assessed associations between gene expression and methylation for genome-wide significant CpGs (n=2802). RESULTS:In total for all analyses, high pesticide exposure was genome-wide significantly (false discovery rate P<0.05) associated with differential DNA methylation of 31 CpGs annotated to 29 genes. Twenty of these CpGs were found in subjects with airway obstruction. Several of the identified genes, for example, RYR1, ALLC, PTPRN2, LRRC3B, PAX2 and VTRNA2-1, are genes previously linked to either pesticide exposure or lung-related diseases. Seven out of 31 CpGs were associated with gene expression levels. CONCLUSIONS:We show for the first time that occupational exposure to pesticides is genome-wide associated with differential DNA methylation. Further research should reveal whether this differential methylation plays a role in the airway disease pathogenesis induced by pesticides.

SUBMITTER: van der Plaat DA 

PROVIDER: S-EPMC5969365 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature

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Occupational exposure to pesticides is associated with differential DNA methylation.

van der Plaat Diana A DA   de Jong Kim K   de Vries Maaike M   van Diemen Cleo C CC   Nedeljković Ivana I   Amin Najaf N   Kromhout Hans H   Vermeulen Roel R   Postma Dirkje S DS   van Duijn Cornelia M CM   Boezen H Marike HM   Vonk Judith M JM  

Occupational and environmental medicine 20180219 6


<h4>Objectives</h4>Occupational pesticide exposure is associated with a wide range of diseases, including lung diseases, but it is largely unknown how pesticides influence airway disease pathogenesis. A potential mechanism might be through epigenetic mechanisms, like DNA methylation. Therefore, we assessed associations between occupational exposure to pesticides and genome-wide DNA methylation sites.<h4>Methods</h4>1561 subjects of LifeLines were included with either no (n=1392), low (n=108) or  ...[more]

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