PON1 and neurodevelopment in children from the chamacos study exposed to organophosphate pesticides in utero

Abstract

Background: Paraoxonase 1 (PON1) detoxifies oxon derivatives of some organophosphate (OP) pesticides, and its genetic polymorphisms influence enzyme activity and quantity. We previously reported that maternal urinary concentrations of dialkyl phosphate (DAP) metabolites, a marker of OP pesticide exposure, were related to poorer mental development and maternally reported symptoms consistent with pervasive developmental disorder (PDD) in 2-year-olds participating in the Center for the Health Assessment of Mothers and Children of Salinas (CHAMACOS) study. Objective: We determined whether PON1 genotypes and enzyme measurements were associated with child neurobehavioral development and whether PON1 modified the association of in utero exposure to OPs (as assessed by maternal DAPs) and neurobehavior. Methods: We measured DAP concentrations in maternal urine during pregnancy, PON1192 and PON1-108 genotypes in mothers and children, and arylesterase (ARYase) and paraoxonase (POase) in maternal, cord, and 2-year-olds' blood. We assessed 353 2-year-olds on the Mental Development Index (MDI) and Psychomotor Development Index (PDI) of the Bayley Scales of Infant Development and queried their mothers on the Child Behavior Checklist to obtain a score for PDD. Results: Children with the PON1-108T allele had poorer MDI scores and somewhat poorer PDI scores. Children were less likely to display PDD when they or their mothers had higher ARYase activity and when their mothers had higher POase activity. Te association between DAPs and MDI scores was strongest in children with PON1-108T allele, but this and other interactions between DAPs and PON1 polymorphisms or enzymes were not significant. Conclusion: PON1 was associated with child neurobehavioral development, but additional research is needed to confirm whether it modifies the relation with in utero OP exposure.