Grantee Research Project Results

2005 Progress Report: Genetics of Phthalate and Bisphenol A Risk in Minority Populations (Individual Susceptibility)

EPA Grant Number: R831711C003
Subproject: this is subproject number 003 , established and managed by the Center Director under grant R831711
(EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).
Center: Center for Research on Early Childhood Exposure and Development in Puerto Rico
Center Director: Alshawabkeh, Akram
Title: Genetics of Phthalate and Bisphenol A Risk in Minority Populations (Individual Susceptibility)
Investigators: Wetmur, James G.
Current Investigators: Wetmur, James G. , Wolff, Mary S. , Chen, Jia
Institution: Mount Sinai School of Medicine
EPA Project Officer: Callan, Richard
Project Period: November 1, 2003 through October 31, 2008 (Extended to October 31, 2010)
Project Period Covered by this Report: November 1, 2004 through October 31, 2005
RFA: Centers for Children's Environmental Health and Disease Prevention Research (2003) RFA Text | Recipients Lists
Research Category: Children's Health , Human Health

Objective:

The objective of this research project is to study seven genetic polymorphisms in the enzymes that activate and detoxify organophosphates and other pesticides in the population of mothers and infants enrolled in project R831711C002.

Progress Summary:

Genotypes and phenotypes have been assessed in 656 samples, including maternal and cord bloods. Genotype-phenotype associations of paraoxonase-1 (PON1) vary by allele, are independent of race/ethnicity, and are stronger for infants than mothers. Results suggest that infants may be more susceptible to toxic effects of PON1 substrates. We have developed a new robust single molecule-based haplotyping technology that was verified by showing haplotype-based variation in PON1 activity in mothers heterozygous at two loci, a result that could not have been determined by genotyping or by haplotype inference. High throughput assays for UGT2B7 and lingual lipase are under development to address our aims to investigate these new endocrine disruptor-related susceptibility factors during the next 3 years.

Future Activities:

We will complete the examination inferred versus molecular PON1 haplotypes in our population. We have found that twenty of the 137 individuals showed different molecular haplotypes than the inferred haplotypes, a 15 percent disconcordance, suggesting caution in the use of statistical inference for haplotypes. When the most probable predicted diplotype had a probability of 50-65 percent, 14 of 31 were discordant (45%). After additional analysis with paraxon as a substrate, these results will be written up for publication.

The UGT2B7 promoters of our African American population will be resequenced. The UGT2B7 results will be compared to exposure measurements and with outcome measurements from project R831711C002.

The lipase/amylase data collection will continue. These data will be used to select individuals with varying lipase/amylase ratios for analysis of phthalate metabolism in collaboration with Dr. Dana Barr at the Centers for Disease Control and Prevention by high performance liquid chromatography-mass spectroscopy (HPLC-MS). We aim to have a large enough sample population to permit the HPLC-MS assays to be carried out in the next year. The goal is to establish an inexpensive biomarker assay to permit large population studies of human variation in phthalate metabolism. The long term goal is to compare these biomarker results with exposure measurements and with outcome measurements from project R831711C002.

Journal Articles:

No journal articles submitted with this report: View all 93 publications for this subproject

Supplemental Keywords:

lipase, paraoxonase, pesticides, haplotyping technology, polymorphisms, endocrine disruptors, EDs, neurodevelopment, minority populations,, RFA, Health, Scientific Discipline, ENVIRONMENTAL MANAGEMENT, POLLUTANTS/TOXICS, Environmental Chemistry, Health Risk Assessment, Chemicals, Endocrine Disruptors - Environmental Exposure & Risk, endocrine disruptors, Biochemistry, Children's Health, Endocrine Disruptors - Human Health, Risk Assessment, environmental health, pesticide exposure, childhood development, pesticides, phtalates, endocrine disrupting chemicals, exposure studies, Human Health Risk Assessment, children's vulnerablity, neurodevelopmental toxicity, genetic polymorphisms, children's environmental health, exposure pathways

Relevant Websites:

http://www.mssm.edu/cpm/dept_research.shtml Exit
http://www.childenvironment.org Exit

Progress and Final Reports:

Original Abstract

Main Center Abstract and Reports:

R831711 Center for Research on Early Childhood Exposure and Development in Puerto Rico

Subprojects under this Center: (EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).
R831711C001 Growing Up Healthy in East Harlem (Community-Based Participatory Research)
R831711C002 Pesticides, Endocrine Disruptors, Childhood Growth and Development (Birth Cohort)
R831711C003 Genetics of Phthalate and Bisphenol A Risk in Minority Populations (Individual Susceptibility)

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The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Conclusions drawn by the principal investigators have not been reviewed by the Agency.