Recent studies demonstrate widespread organophosphate pesticide (OP) exposures to pregnant women and children. However, given the same exposure, some individuals may be more susceptible to the adverse effects of OPs depending on their genetic makeup and expression of genes encoding key metabolic enzymes. For example, the human enzyme paraoxonase (PON1) detoxifies various OPs with different efficiency depending on the main polymorphism at position 192 and others along promoter and coding regions. As part of the CHAMACOS longitudinal birth cohort study, we have investigated OP exposures and health effects in -500 pregnant Latina women and their children living in the agricultural community of the Salinas Valley, CA. Initial data suggest that OP exposure in this cohort exceed national reference levels, and that maternal OP urinary metabolite levels were associated with shortened gestation and abnormal reflexes in neonates. Preliminary data from 130 maternal and cord blood samples show that newborns had lower PON1 activity than their mothers, suggesting they may be more susceptible to the adverse effects of OPs. Thus, differences in genotype, enzyme activity, and age may contribute to differential sensitivity to OP exposures. In the proposed study, we will take advantage of an extensive biorepository and data on growth and neurodevelopment from the CHAMACOS cohort. Our objectives are: 1) to create a PON1 gene haplotype map for this Latino population; 2) to examine the ontogeny of PON1 enzyme activity in infants from birth through 24 months; 3) to establish whether PON1 genotype is associated with OP pesticides in maternal and cord blood; and 4) to determine whether PON1 modifies the relationship of OP exposure and fetal growth, length of gestation and neurodevelopment. To address these aims, we will genotype CHAMACOS mothers and children for five PON1 polymorphisms (192, 55, -108, -909, -162); measure four substrate-specific PON1 enzyme activities (arylesterase, paraoxonase, diazoxonase, chlorpyrifos oxonase) in maternal, cord and child blood at 12 and 24 months; and measure OPs in cord and maternal bloods. This study will help identify human subpopulations more susceptible to the health impact of OP exposure. These data will support planning for the National Children's Study, identify subpopulations susceptible to chemical warfare agents, and inform policy decisions for implementation of the Food Quality Protection Act. ? ? ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Research Project (R01)
Project #
1R01ES012503-01A1
Application #
7047257
Study Section
Special Emphasis Panel (ZRG1-HOP-Q (90))
Program Officer
Gray, Kimberly A
Project Start
2006-01-18
Project End
2010-12-31
Budget Start
2006-01-18
Budget End
2006-12-31
Support Year
1
Fiscal Year
2006
Total Cost
$361,000
Indirect Cost
Name
University of California Berkeley
Department
Public Health & Prev Medicine
Type
Schools of Public Health
DUNS #
124726725
City
Berkeley
State
CA
Country
United States
Zip Code
94704
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