Karen Huen, Kim Harley, Jordan Brooks, Alan Hubbard, Asa Bradman, Brenda Eskenazi, Nina Holland
Abstract
Background: Paraoxonase 1 (PON1) is an enzyme that detoxifies activated organophosphorous
(OP) pesticides and is also involved in oxidative stress pathways.
Objectives: PON1 activity in newborns is lower than in adults however the ontogeny of PON1
activity is poorly characterized in young children. We examined the effects of age and
PON1genotypes on enzyme activity in a birth cohort of Mexican-American children.
Methods: Three substrate-specific measures of PON1 activity were determined in 1143 plasma
samples collected longitudinally from 458 children at five time points from birth through seven
years of age.
PON1 polymorphisms at positions 192 and -108 were also genotyped in thesechildren.
Results: Contrary to previous reports that PON1 activities plateau by age two, we observed an
age-dependent increase in all three PON1 measures from birth through age seven (p<0.0001).
The
PON1192 genotype significantly modified the effect of age on paraoxonase (POase) activity;p<0.0001) such that increases in enzyme activity with age were influenced by the number of R
alleles in a dose dependent manner. Children with the
PON1-108CC192RR diplotype hadsignificantly higher mean PON1 activities and also experienced steeper increases of POase
activity over time compared to children with the
PON1-108TT192QQ diplotype.
Conclusions: Lower levels of the PON1 enzyme, which is involved in protection against OPs and
oxidative stress, persist in young children past age two through at least age seven. Future
policies addressing pesticide exposure in children should take into account that the window of
vulnerability to OPs in young children may last beyond infancy.
