Functional Genomics PON1 Study

This study examines how our individual genetic makeup influences our susceptibility to chemical exposures.  This study focuses on the PON1 gene, which impacts the body’s ability to detoxify organophosphate pesticides and eliminate them from the body.

PON1 Study Findings – click hereWhat Is PON1?

The structure of the PON1 enzyme (Copyright 2011, Discovery Medicine)

The body interprets the genetic code of the PON1 gene in order to make the PON1 enzyme. The PON1 enzyme is a biological macromolecule that acts as the body’s first line of defense against exposure by breaking down harmful organophosphate (OP) pesticides that enter the body. Additionally, recent studies suggest PON1 may also have antioxidant properties.  The PON1 enzyme’s ability to detoxify OPs in the body can be altered by genetic factors and is less effective at young ages.

How the PON1 Enzyme Works – click here

Differential Susceptibility:

  • Differences (or polymorphisms) in the base pair code of the PON1 gene affect the level and/or activity of PON1 enzymes in the body.
  • An individual’s “PON1 status” is a characterization of both their PON1 genetic code and the level and activity of the PON1 enzyme that is made from the PON1 gene.
  • One’s PON1 status has an effect on the body’s ability to defend itself against exposure to OP pesticides.

What the PON1 Study Investigates:

  • How the genetic code for the PON1 enzyme affects how the body responds to organophosphate (OP) pesticide exposure.
  • The relationship of factors like age, gender, and ethnicity with PON1 status.
  • Frequencies of PON1 genetic polymorphisms and phenotype in pregnant women and their children.
  • Whether maternal factors, including genotype and PON1 expression, affect children’s PON1 status.
  • The development of PON1 activity in children as they age.
  • Whether PON1 status modifies the relationship of exposure with growth and neurodevelopment in children.
  • Whether there are ethnic and gender differences in frequencies of PON1 genetic polymorphisms and PON1 phenotype.
  • The role of promoter and other polymorphisms in PON1 status in humans.

Data Collection:

  • Genetic and enzyme analyses were run in blood samples collected as part of the CHAMACOS Cohort biological sample collection (Learn about CHAMACOS Study Participants here).
  • PON1 Genetic and Enzyme Analyses:
    • Many genetic polymorphisms of the PON1 gene have been identified and several have been reported to affect either enzyme activity or enzyme levels. The detoxifying efficiency of the PON1 enzyme depends on the genetic polymorphisms PON1192 (QQ <QR<RR). PON1 status, or activity, is a function of PON1192 genotype and enzyme quantity. Several promoter region polymorphisms including PON1-108 are associated with variation in levels of enzyme.
  • Substrate-specific assays are used to measure PON1 enzyme quantity and activity.  The arylesterase assay is used to measure PON1 levels (quantity).  The oxon derivatives of OP pesticides chlorpyrifos and parathion are used as substrates for the chlorpyrifos-oxonase (CPOase) and paraoxonase (POase) assays, which reflect PON1 substrate-specific activity.

Research Team:

  • Nina Holland, PhD
  • Brenda Eskenazi, PhD
  • Karen Huen Northcote, PhD
  • Lisa Barcellos, PhD
  • Asa Bradman, PhD
  • Kim Harley, PhD
  • Pin Xiang
  • Michelle Vedar Gubatina, MPH

 

Funded by: Duration: Study Contact:
  • The National Institute for Environmental  Health Sciences (NIEHS)
  • U.S. Environmental Protection Agency (EPA)
2006-2011,  ongoing Nina Holland, PhD
Director, CERCH Biorepository and Children’s Environmental Health Laboratory
ninah@berkeley.edu

510-665-2200
Print This Page Print This Page