The association between organophosphate pesticide exposure and methylation of paraoxonase-1 in children with attention-deficit/hyperactivity disorder (vol 171, 107702, 2023)

Exposure to organophosphate pesticides (OPPs) is ubiquitous and has been reported to interfere with neurodevelopment in children. OP compounds are metabolized by paraoxonase 1 (PON1), and interindividual differences in susceptibility to OP exposure are brought out by the genetic polymorphism and epigenetic modifications of PON1. DNA methylation is a common epigenetic modification that can regulate the expression of PON1. We have previously identified that PON1 single nucleotide polymorphisms are associated with OP levels and ADHD risk in children. This study aims to elucidate whether changes in PON1 DNA methylation levels due to OP exposure and genetic polymorphism could increase ADHD risk in children. A total of 181 children participated in this case-control study, including 85 children with ADHD and 96 children as control. We measured urinary concentrations of OP metabolites, dialkyl phosphate (DAP), including dimethyl alkylphosphate (DM) and diethyl alkylphosphate (DE) in children. The changes in DNA methylation levels in the proximal promoter region of PON1 were examined. The results showed that ADHD children had higher dimethyl phosphate (DMP) levels (238.95 nmol/g cre. vs. 164.83 nmol/g cre.; p-value, 0.01) and lower methylation levels (22 out of 25 CpG sites; p-value <0.05) than the control children. The mean methylation levels were 43.14 +/- 11.44% for the ADHD group and 50.19 +/- 13.74% for the control group (p-value <0.05). We observed a negative association between OP metabolites and mean methylation levels (beta = -0.06, 95% CI = -0.09, -0.02). The mediation analysis showed a marginal significant mediation by PON1 methylation levels in the association between OPPs exposure and ADHD. These results imply that chronic sub-acute OPPs exposure could influence the PON1 methylation levels. This study expands our understanding of the relationship between exposure to OPPs, neurobehavior in children, and the role of PON1 DNA methylation and warrants further research.

Automated summary

This study aimed to investigate the relationship between exposure to organophosphate pesticides (OPPs) and the risk of attention deficit hyperactivity disorder (ADHD) in children. The results showed that children with ADHD had higher levels of OP metabolites and lower levels of PON1 methylation than the control group, suggesting that chronic sub-acute exposure to OPPs could influence PON1 methylation levels.