PON1 and Neurodevelopment in Children

Sept. 7, 2010, 8:21 a.m.

 

Brenda Eskenazi, Karen Huen, Amy Marks, Kim G. Harley, Asa Bradman, Dana Boyd Barr, Nina Holland

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 (DAPs) metabolites, a marker of OP pesticide exposure, were related to poorer mental development and maternally-reported symptoms consistent with pervasive developmental disorder (PDD) in two-year olds participating in the 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 organophosphates (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 two-year old’s blood. We assessed 353 two-year olds on the Mental Development (MDI) and Psychomotor Development Indices (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 and somewhat poorer Psychomotor Development Index scores. Children were less likely to display PDD when they or their mothers had higher ARYase and when their mothers had higher POase activities. The association between DAPs and MDI 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 if it modifies the relation with in utero organophosphate exposure.

 

http://ehp03.niehs.nih.gov/article/info%3Adoi%2F10.1289%2Fehp.1002234

 

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