PON1 as a biomarker of susceptibility to pesticide exposure in Mexican-American children: Implications for public health

Recent studies demonstrate widespread exposures of women and children to organophosphate (OP) pesticides. In the longitudinal birth cohort study of low-income Mexican-American farmworker families (CHAMACOS) we found that in utero exposures to pesticides were associated with abnormal birth and neurodevelopmental outcomes. However, given the same level of exposure, some individuals may be more susceptible to adverse health effects than others depending on genetic makeup and expression of genes encoding metabolic enzymes. For instance, paraoxonase 1 (PON1), which can detoxify OPs, provides an example of a metabolic enzyme whose broad variability within populations may confer differential susceptibility to environmental exposures. Someone with low PON1 levels may be less protected from OP exposures than people with higher PON1 levels. In this study, we sought to characterize which factors might affect PON1 variability and thus susceptibility to OPs. We determined PON1 genotypes and three PON1 enzyme activities in more than 450 mothers and their children from pregnancy through age 9. Several genetic polymorphisms were associated with lower PON1 expression. Although it was previously thought that children's PON1 levels reach adult ones by age 2, we found that PON1 levels and activities were the lowest in newborns and steadily increased with age. However, they remained below adult levels up to 7 years. These findings highlight several factors affecting PON1 and enable identification of vulnerable subpopulations. Infants and young children, particularly those with PON1 genotypes encoding for lower PON1 levels and activities, have up to 65-fold lower levels of the protective PON1 enzyme than adults and may be especially susceptible to OP exposures. Our data suggest that the window of increased vulnerability to OP pesticides in young children may persist beyond infancy through age 7. Future policies addressing pesticide exposure in pregnant women and children should take into account protection of these at risk populations.