PON1 DNA methylation and neurobehavior in Mexican-American children with prenatal organophosphate exposure

Abstract

PON1 is a multifunctional enzyme involved in oxidative stress and detoxification of some organophosphate (OP) pesticides. It has been associated with nervous system diseases like Alzheimer's disease, amyotrophic lateral sclerosis, Parkinson's disease, and autism. We previously found that PON1 susceptible genotypes were associated with lower IQ scores in children. Epigenetic marks, such as DNA methylation, can regulate gene expression. Yet, data on whether DNA methylation may influence the relationship between PON1 levels and neurobehavior are limited. In this study, we used Illumina 450K and EPIC BeadChip arrays to assess PON1 DNA methylation in blood specimens collected from children (n = 238) at birth (cord blood) and age 7 years and examined their relationship with cognitive outcomes. The Wechsler Intelligence Scale for Children was used to assess Full Scale IQ and four composite measures (Verbal Comprehension, Perceptual Reasoning, Working Memory, and Processing Speed Indexes) in 7-year-old children. We observed a consistent yet nonsignificant inverse relationship of methylation at several CpG sites close to the PON1 transcription start site with Full Scale IQ and other composite measures of cognition. We also found an inverse relationship between cord blood methylation at cg15887283 with working memory and a positive association of 7-year-old methylation at cg22798737 with processing speed, independent of OP exposure. However, none of the associations remained significant after accounting for multiple comparisons. This study provides some evidence of the role DNA methylation may play in the known relationship between PON1 and neurobehavior in children, however it appears to be only suggestive and warrants additional research.