Genetics of Phthalate /Bisphenol Risk in Minority Groups

少数群体邻苯二甲酸盐/双酚风险的遗传学

• 批准号: 6960220
• 负责人: James G Wetmur
• 金额: $ 10万
• 依托单位: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-05-07 至 2008-10-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6960220
• 关键词: African American; Hispanic Americans; caucasian American; child (0-11); child physical development; child psychology; clinical research; detoxification; developmental neurobiology; environmental toxicology; enzyme activity; gene environment interaction; genetic polymorphism; genotype; glucuronosyltransferase; human subject; lipase; neurotoxicology; phenols; phenotype; phthalates; plastics; polymerase chain reaction; racial /ethnic difference; toxin metabolism; urinalysis

Description (provided by applicant): The overall goal of this molecular genetic project is to assess gene?environment interactions that may influence individual susceptibility to the EDs and developmental neurotoxicants that are the overall scientific theme of this Center. The plan is to meet this objective by identifying and characterizing polymorphisms and variations in expression levels of PON1, lipase and UGT-glucuronosyltransferase, all involved in the metabolism and detoxification of EDs and pesticides. The specific aims of this application are, Phthalates: 1) examine salivary lipase activity as a biomarker for conversion of phthalate diesters to phthalate monoesters; 2) determine expression levels of the three linked human lipase genes in human salivary glands; 3) determine racial/ethnic differences in the frequencies of the common polymorphisms in the salivary human lipase gene(s) and in salivary lipase activity; 4) examine salivary lipase activity in relation to urinary levels of phthalate metabolites; 5) examine salivary lipase polymorphisms and haplotypes in relation to urinary levels of phthalate metabolites; 6) obtain pilot data on the extent of glucuronidation of phthalate monoesters in urine; and 7) collaborate with the epidemiology project (Project 2) to examine association of lipase genotype and phenotype with child developmental outcomes. Bisphenol A: 1) genotype the common missense polymorphism in human UGT2B7 in our population of African-Americans, Caucasians and Hispanics and its association with urinary metabolites; 2) identify and assess common promoter, coding region and splice-site polymorphisms in human UGT2B7 in our African-Americans, Caucasians and Hispanics, establish the common haplotypes, and their association with exposure; and 3) collaborate with Project 2 to examine human UGT2B7 genotype/haplotype effects on developmental outcomes. Continuing PON1 phenotype?genotype studies: 1) determine high-density lipid (HDL) levels for the existing birth cohort and carry out a detailed genotype?phenotype reanalysis, 2) genotype and haplotype new members of the extended birth cohort for PON1 polymorphisms; and 3) collaborate with Project 2 to examine PON1 genotype and phenotype effects on developmental outcomes.

描述（由申请人提供）：该分子遗传项目的总体目标是评估基因的环境相互作用，可能会影响个人对ED的易感性和 发育性神经毒性是该中心的总体科学主题。该计划是通过确定和表征PON1，脂肪酶和UGT-葡萄糖基转移酶的表达水平的多态性和表达水平的变化来实现这一目标，这些都参与了EDS和农药的代谢和解毒。该应用的具体目的是，邻苯二甲酸盐：1）检查唾液脂肪酶活性作为将邻苯二甲酸酯二乳液转化为邻苯二甲酸酯单植物的生物标志物； 2）确定人类唾液腺中三个连接的人脂肪酶基因的表达水平； 3）确定唾液人脂肪酶基因和唾液脂肪酶活性中常见多态性频率的种族/种族差异； 4）检查与邻苯二甲酸酯代谢产物尿液水平有关的唾液脂肪酶活性； 5）检查唾液脂肪酶多态性和单倍型相对于邻苯二甲酸酯代谢产物的尿水水平； 6）获取有关尿液中邻苯二甲酸酯单植物葡萄糖醛酸化程度的试验数据； 7）与流行病学项目（项目2）合作，检查脂肪酶基因型和表型与儿童发育结果的关联。 Bisphenol A：1）基因型在我们的非裔美国人，高加索人和西班牙裔人群中，人类UGT2B7中常见的错义多态性，以及与泌尿代谢物的关联； 2）在我们的非裔美国人，高加索人和西班牙裔中，在人类UGT2B7中识别和评估共同的启动子，编码区和剪接位点多态性，建立了共同的单倍型及其关联 暴露； 3）与项目2合作检查人类UGT2B7基因型/单倍型 对发展结果的影响。持续PON1表型？基因型研究：1）确定现有出生队列的高密度脂质（HDL）水平，并进行详细的基因型？表型重新分析，2）PON1多构态的基因型和单型新成员； 3）与项目2合作，检查PON1基因型和表型对发育结果的影响。