Abstract
Introduction: We previously showed that occupational exposure to pesticides is associated with lower lung function levels (FEV1 and FEV1/FVC) and higher prevalence of airway obstruction. However, the mechanisms through which pesticides influence disease pathogenesis are still largely unknown. We hypothesized that pesticide exposure is associated with differential DNA methylation.
Aim: To investigate associations between occupational exposure to pesticides and genome-wide DNA methylation.
Methods: We included 1561 subjects of the LifeLines study cohort 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 the Illumina 450K array. Associations between pesticide exposure and 430,950 methylation sites (CpGs) were assessed using robust linear regression adjusted for sex, age, pack-years, smoking status, batch effects and % cell types.
Results: High pesticide exposure was associated with differential methylation of 6 CpGs (p<10-5). The top CpG (cg02286193 near ESRRB) was hypomethylated in highly exposed subjects and the other CpGs were hypermethylated. Two of the CpGs (i.e. cg03181524 in RYR1 and cg02393030 in NDFIP2) were annotated to genes previously associated with pesticide mechanisms of action.
Conclusions: For the first time, we show that occupational exposure to pesticides is associated with differential DNA methylation. Further research should indicate whether this mechanism plays a role in the pathogenesis of airway obstruction.
- Copyright ©the authors 2016
