RT Journal Article
SR Electronic
T1 Occupational exposure to pesticides is associated with differential DNA methylation
JF Occupational and Environmental Medicine
JO Occup Environ Med
FD BMJ Publishing Group Ltd
SP 427
OP 435
DO 10.1136/oemed-2017-104787
VO 75
IS 6
A1 Diana A van der Plaat
A1 Kim de Jong
A1 Maaike de Vries
A1 Cleo C van Diemen
A1 Ivana Nedeljković
A1 Najaf Amin
A1 Hans Kromhout
A1 Biobank-based Integrative Omics Study Consortium
A1 Roel Vermeulen
A1 Dirkje S Postma
A1 Cornelia M van Duijn
A1 H Marike Boezen
A1 Judith M Vonk
YR 2018
UL http://oem.bmj.com/content/75/6/427.abstract
AB 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.