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2007 Progress Report: Genetics of Phthalate and Bisphenol A Risk in Minority Populations (Individual Susceptibility)
EPA Grant Number: R831711C003Subproject: 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: Mount Sinai Center for Children’s Health and the Environment
Center Director: Wolff, Mary S.
Title: Genetics of Phthalate and Bisphenol A Risk in Minority Populations (Individual Susceptibility)
Investigators: Wetmur, James G.
Institution: Mount Sinai School of Medicine
EPA Project Officer: Fields, Nigel
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)
Research Category: Children's Health , Health Effects
Description:
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
| Other subproject views: | All 155 publications | 93 publications in selected types | All 84 journal articles |
| Other center views: | All 170 publications | 98 publications in selected types | All 88 journal articles |
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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. |
R831711C002 (2007) R831711C003 (2007) |
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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) R831711C003 (2007) |
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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) R831711C001 (2006) R831711C002 (2006) R831711C003 (2006) R831711C003 (2007) |
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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) R831711C001 (2006) R831711C002 (2006) R831711C002 (2007) R831711C003 (2006) R831711C003 (2007) |
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Wolff, MS, Engel SM, Berkowitz GS, Ye X, Silva MJ, Zhu C, Wetmur JG, Calafat AM. Prenatal phenol and phthalate exposures and birth outcomes. Environmental Health Perspectives 2008;116(8):1092-1097. |
R831711 (2007) R831711C003 (2007) |
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, POLLUTANTS/TOXICS, ENVIRONMENTAL MANAGEMENT, Scientific Discipline, Health, RFA, Endocrine Disruptors - Environmental Exposure & Risk, Risk Assessment, Health Risk Assessment, endocrine disruptors, Chemicals, Children's Health, Biochemistry, Environmental Chemistry, Endocrine Disruptors - Human Health, neurodevelopmental toxicity, endocrine disrupting chemicals, children's environmental health, childhood development, exposure pathways, pesticide exposure, genetic polymorphisms, environmental health, phthalates, phtalates, pesticides, children's vulnerablity, exposure studies
Progress and Final Reports:
2004 Progress Report
2005 Progress Report
2006 Progress Report
Original Abstract
Main Center Abstract and Reports:
R831711 Mount Sinai Center for Children’s Health and the Environment