Organophosphate pesticide exposure and differential genome-wide DNA methylation.

ABSTRACT: BACKGROUND:Organophosphates (OP) are widely used insecticides that acutely inhibit acetylcholinesterase enzyme activity. There is great interest in improving the understanding of molecular mechanisms related to chronic OP exposure induced toxicity. We aim to elucidate epigenetic changes associated with OP exposure, using untargeted analysis of genome-wide DNA methylation data. METHODS:In a population-based case control study of Parkinson's disease (PD), we assessed ambient OP exposure via residential and workplace proximity to commercial applications. We investigated associations between OP exposure and genome-wide DNA methylation (Illumina 450?k) in 580 blood samples (342 PD patients, 238 controls) and 259 saliva samples (128 patients, 131 controls). To identify differential methylation related to OP exposure, we controlled for age, sex, European ancestry, and PD status; in addition, we stratified by disease status. RESULTS:We identified 70 genome-wide significant CpGs, including cg01600516 in ALOX12 (cor?=?0.27, p?=?1.73E-11) and two CpGs in HLA genes, cg01655658 (cor?=?-0.24, p?=?2.80E-09) in HLA-L (pseudogene) and cg15680603 (cor?=?0.20, p?=?7.94E-07) in HLA-DPA1. Among the 70 CpGs located in 41 genes, 14 were also differentially methylated in saliva samples. The most overrepresented pathway was the nicotinic acetylcholine receptor signaling pathway (fold enrichment?=?15.63, p?=?1.01E-03, FDR?=?1.64E-01). Expanding to a larger number of genes (CpG p?

SUBMITTER: Paul KC 

PROVIDER: S-EPMC6400463 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature