Grantee Research Project Results

2007 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, 2006 through October 31,2007
RFA: Centers for Children's Environmental Health and Disease Prevention Research (2003) RFA Text | Recipients Lists
Research Category: Children's Health , Human Health

Objective:

Project 3 has been studying the influence of genetic variability on the metabolism and health effects of organophosphate pesticides, phenols and phthalates.

Progress Summary:

The genetic study of organophosphate metabolism involved seven genetic polymorphisms in the population of mothers and infants enrolled in Project 2. Genotypes and phenotypes have been assessed in 656 samples, including maternal and cord bloods. Genotype/haplotype-phenotype associations of 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, and that fetal development may be impaired if maternal PON1 or genotype are low-activity. 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.

The genetic study of phenol metabolism involved determination of the effect of the common missense polymorphism in human UGT2B7 in the same population of mothers enrolled in Project 2. The urinary metabolites were measured at the CDC.

We characterized 9 phenols in urine and associations with the UDP-glucuronosyltransferase 2B7 (UGT2B7) His²⁶⁸Tyr polymorphism as well as population characteristics as predictors of their concentrations. Total urinary concentrations of phenolic metabolites were measured in 367 pregnant women in a New York City cohort. Multivariate analyses were conducted to identify predictors of phenol urinary metabolite concentrations including polymorphism in the UGT2B7 gene, ethnicity, socioeconomic status and use of consumer products. Bisphenol A, 2-hydroxy-4-methoxybenzo-phenone, triclosan, 2,4- and 2,5-dichlorophenol (DCP) were detected in at least 78% of samples. Median concentration of 2,5-DCP was 52.9 μg/L, with an adjusted geometric mean of 165 μg/L for mothball users. Differences by race/ethnicity were seen in 2,4-DCP and 2,5-DCP concentrations in adjusted models. UGT2B7 Tyr²⁶⁸ allele carriers had lower bisphenol A and triclosan urinary concentrations than non-carriers (p<0.05). This study represents the first systematic evaluation of phenolic metabolites in pregnant women. Five of the nine metabolites were detected in more than three quarters of women. Product use as well as individual metabolism may influence urinary concentrations of these chemicals. We are continuing to analyze these data and will publish our results soon.

The genetic study of phthalate metabolism involved determination of the effect of the common missense polymorphism in human UGT2B7 as well as 14 tagging SNPs for the lipase genes encoding the first enzymes in phthalate metabolism, again in the same population of mothers enrolled in Project 2. The urinary metabolites were again measured at the CDC.

We have observed metabolic effects of polymorphisms in both UGT2B7 and lipase. We are continuing to analyze these data and will publish our results soon.

In new work aimed at establishing a new biomarker of exposure, we have studied loss of imprinting in human placenta. The assay is complete, and application in association studies is under way.

Journal Articles on this Report : 5 Displayed | Download in RIS Format

Publications Views
Other subproject views:	All 93 publications	57 publications in selected types	All 52 journal articles
Other center views:	All 256 publications	143 publications in selected types	All 120 journal articles

Publications
Type	Citation	Sub Project	Document Sources
Journal Article	Engel SM, Berkowitz GS, Barr DB, Teitelbaum SL, Siskind J, Meisel SJ, Wetmur JG, Wolff MS. Prenatal organophosphate metabolite and organochlorine levels and performance on the Brazelton Neonatal Behavioral Assessment Scale in a multiethnic pregnancy cohort. American Journal of Epidemiology 2007;165(12):1397-1404.	R831711 (2007) R831711 (Final) R831711C002 (2007) R831711C003 (2007)	Abstract from PubMed Full-text: Oxford-Full Text HTML Exit Abstract: Oxford-Abstract Exit Other: Oxford-Full Text PDF Exit
Journal Article	Lambertini L, Diplas AI, Lee MJ, Sperling R, Chen J, Wetmur J. A sensitive functional assay reveals frequent loss of genomic imprinting in human placenta. Epigenetics 2008;3(5):261-269.	R831711 (2007) R831711 (Final) R831711C003 (2007)	Full-text from PubMed Abstract from PubMed Associated PubMed link Full-text: Landes Bioscience-Full Text PDF Exit Abstract: Landes Bioscience-Abstract Exit
Journal Article	Wallenstein S, Chen J, Wetmur JG. Comparison of statistical models for analyzing genotype, inferred haplotype, and molecular haplotype data. Molecular Genetics and Metabolism 2006;89(3):270-273.	R831711 (2005) R831711 (2006) R831711 (2007) R831711 (Final) R831711C001 (2006) R831711C002 (2006) R831711C003 (2006) R831711C003 (2007)	Abstract from PubMed Abstract: ScienceDirect-Abstract Exit
Journal Article	Wolff MS, Engel S, Berkowitz G, Teitelbaum S, Siskind J, Barr DB, Wetmur J. Prenatal pesticide and PCB exposures and birth outcomes. Pediatric Research 2007;61(2):243-250.	R831711 (2005) R831711 (2006) R831711 (2007) R831711 (Final) R831711C001 (2006) R831711C002 (2006) R831711C002 (2007) R831711C003 (2006) R831711C003 (2007)	Abstract from PubMed Full-text: Nature-Full Text HTML Exit Abstract: Nature-Abstract Exit Other: Nature-Full Text PDF Exit
Journal Article	Wolff, MS, Engel SM, Berkowitz GS, Ye X, Silva MJ, Zhu C, Wetmur J, Calafat AM. Prenatal phenol and phthalate exposures and birth outcomes. Environmental Health Perspectives 2008;116(8):1092-1097.	R831711 (2007) R831711 (Final) R831711C003 (2007)	Full-text from PubMed Abstract from PubMed Associated PubMed link

Supplemental Keywords:

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

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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