title: Developmental changes in PON1 enzyme activity in young children and effects of PON1 polymorphisms.
abstract: BACKGROUND
  Paraoxonase 1 (PON1) is an enzyme that detoxifies activated organophosphorus pesticides (OPs) and is also involved in oxidative stress pathways.
  
  
  OBJECTIVE
  PON1 activity in newborns is lower than in adults, but the ontogeny of PON1 activity is poorly characterized in young children. We examined the effects of age and PON1 genotype on enzyme activity in a birth cohort of Mexican-American children.
  
  
  METHODS
  We determined three substrate-specific measures of PON1 activity in 1,143 plasma samples collected longitudinally from 458 children at five time points from birth through 7 years of age, and genotyped PON1 polymorphisms at positions 192 and -108 in these children.
  
  
  RESULTS
  Contrary to previous reports that PON1 activities plateau by 2 years of age, we observed an age-dependent increase in all three PON1 measures from birth through 7 years of age (p < 0.0001). The PON1(192) 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 had significantly higher mean PON1 activities and also experienced steeper increases of POase activity over time compared with 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 2 years of age through at least 7 years of age. 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.
authors.affiliation: Center for Children's Environmental Health, School of Public Health, University of California, Berkeley, California, USA.
authors.forename: Karen
authors.initials: K
authors.lastname: Huen
authors.forename: Kim
authors.initials: K
authors.lastname: Harley
authors.forename: Jordan
authors.initials: J
authors.lastname: Brooks
authors.forename: Alan
authors.initials: A
authors.lastname: Hubbard
authors.forename: Asa
authors.initials: A
authors.lastname: Bradman
authors.forename: Brenda
authors.initials: B
authors.lastname: Eskenazi
authors.forename: Nina
authors.initials: N
authors.lastname: Holland
mesh_terms: D000367:Age Factors; D043303:Aryldialkylphosphatase / Q000235:genetics* / Q000378:metabolism*; D002648:Child; D002675:Child, Preschool; D005260:Female; D018507:Gene Expression Regulation, Developmental; D005838:Genotype; D006801:Humans; D007223:Infant; D008297:Male; D011110:Polymorphism, Genetic / Q000235:genetics*
chemical_list: D043303:Aryldialkylphosphatase