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Developmental changes in PON1 enzyme activity in young children and effects of PON1 polymorphisms

Karen Huen1, Kim Harley, Jordan Brooks

  • 1Center for Children's Environmental Health, School of Public Health, University of California, Berkeley, California, USA.

Environmental Health Perspectives
|December 19, 2009
PubMed

Insights

Paraoxonase 1 (PON1) enzyme activity increases with age in children up to 7 years, contrary to prior beliefs. PON1 genotype influences this increase, impacting protection against organophosphorus pesticides.

Area of Science:

  • Biochemistry and Environmental Health
  • Pediatric Metabolism and Toxicology

Background:

  • Paraoxonase 1 (PON1) is a key enzyme for detoxifying organophosphorus pesticides (OPs).
  • PON1 also plays a role in oxidative stress pathways, crucial for understanding toxicological responses.
  • PON1 activity is known to be lower in newborns than adults, but its developmental trajectory in early childhood is not well understood.

Purpose of the Study:

  • To investigate the ontogeny of PON1 enzyme activity in young children.
  • To examine how age and PON1 genotype influence PON1 activity in a Mexican-American birth cohort.

Main Methods:

  • Longitudinal analysis of 1,143 plasma samples from 458 children from birth to 7 years.
  • Measurement of three substrate-specific PON1 activities at five time points.
  • Genotyping of PON1 polymorphisms at positions 192 and -108.

Main Results:

  • PON1 activity demonstrated a significant age-dependent increase from birth through 7 years, contradicting previous findings of early plateauing.
  • The PON1(192) genotype significantly modulated paraoxonase (POase) activity, with a dose-dependent effect of R alleles on age-related increases.
  • Children with the PON1(-108CC192RR) diplotype exhibited higher mean PON1 activities and steeper increases in POase activity over time compared to those with the PON1(-108TT192QQ) diplotype.

Conclusions:

  • Reduced PON1 enzyme levels, important for OP detoxification and oxidative stress management, persist in children beyond 2 years of age, extending to at least 7 years.
  • The window of vulnerability to organophosphorus pesticide exposure in children may be longer than previously assumed, extending beyond infancy.
  • Public health policies concerning pesticide exposure in children should consider this prolonged period of lower protective enzyme activity.
Abstract

Keywords:
PON1 activityagechildrenenzymatic assaylongitudinal birth cohortorganophosphate metabolismoxidative stressparaoxonasepesticides

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