PON1 and neurodevelopment in children from the CHAMACOS study exposed to organophosphate pesticides in utero.
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. The 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.


CONCLUSIONS
PON1 was associated with child neurobehavioral development, but additional research is needed to confirm whether it modifies the relation with in utero OP exposure.
Center for Environmental Research and Children's Health, School of Public Health, University of California, Berkeley, Berkeley, California 94602, USA. eskenazi@berkeley.edu
Brenda
B
Eskenazi
Karen
K
Huen
Amy
A
Marks
Kim G
KG
Harley
Asa
A
Bradman
Dana Boyd
DB
Barr
Nina
N
Holland
D000293:Adolescent; D000328:Adult; D043303:Aryldialkylphosphatase / Q000235:genetics / Q000378:metabolism*; D001526:Behavioral Symptoms / Q000208:ethnology; D001921:Brain / Q000196:embryology / Q000201:enzymology / Q000254:growth & development*; D002140:California / Q000208:ethnology; D002653:Child Behavior Disorders / Q000208:ethnology; D002657:Child Development / Q000187:drug effects*; D002675:Child, Preschool; D004781:Environmental Exposure / Q000032:analysis / Q000706:statistics & numerical data; D005260:Female; D006801:Humans; D008658:Inactivation, Metabolic; D007223:Infant; D007231:Infant, Newborn; D018811:Maternal Exposure / Q000706:statistics & numerical data; D017058:Mexican Americans / Q000208:ethnology; D009749:Nutrition Surveys; D009943:Organophosphorus Compounds / Q000652:urine*; D010575:Pesticides / Q000652:urine*; D011247:Pregnancy; D055815:Young Adult
D009943:Organophosphorus Compounds; D010575:Pesticides; D043303:Aryldialkylphosphatase; C468406:PON1 protein, human