Genetic Biomarkers of Polybrominated Biphenyl (PBB)

多溴联苯 (PBB) 的遗传生物标志物

基本信息

批准号：
8965041
负责人：
Karen Conneely
金额：
$ 48.28万
依托单位：
EMORY UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-09-30 至 2019-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8965041
关键词：
Affect Area Biological Body fat Candidate Disease Gene Chemicals Child Complex DNA Methylation Data Data Set Detection Development Eating Endocrine Endocrine Disruptors Ensure Environment Environmental Exposure Epigenetic Process Excretory function Exposure to Farming environment Flame Retardants Food Food Supply Functional disorder Genes Genetic Genetic Markers Genetic Polymorphism Genetic Variation Genome Genomic Segment Genotype Goals Growth and Development function Half-Life Health Hormones Human Individual Industrial Accidents Leukocytes Life Link Longevity Measures Metabolism Methylation Michigan Molecular National Health and Nutrition Examination Survey Pathway interactions Pattern Polybrominated Biphenyls Population Population Control Predisposition Research Rural Serum Site Source Staging Thyroid Function Tests Thyroid Gland Time Variant Work age difference base bead chip chemical property cohort consumer product design environmental chemical exposure epigenetic regulation epigenetic variation epigenome experience genetic variant genome wide association study genome-wide insight lipid metabolism member methylation pattern pubertal timing public health relevance

项目摘要

DESCRIPTION (provided by applicant): Humans are exposed to chemicals such as brominated flame retardants (BFRs) at unprecedented levels, and a wide variety of health effects are attributed to such exposures. However, the biological mechanisms that link exposures to its consequences remain unknown. An industrial accident in the 1970's exposed over 4000 individuals in rural Michigan to polybrominated biphenyl (PBB), a BFR that was present in the food supply for years prior to detection and management. Health effects are still evident in these individuals and their children. Because this population has been assessed regularly since the exposure, it is an ideal group in which to examine the molecular mechanisms that contribute to susceptibility, vulnerability and health effects. The project goals are to: 1) identify the genetic variants that associate with the rate of PBB elimination over time, 2) identif epigenetic patterns that associate with PBB exposure, 3) integrate genetic and epigenetic datasets and identify complex gene-environment relationships in PBB exposed individuals and 4) evaluate the contribution PBB-associated genetic and epigenetic factors to endocrine-related consequences of exposure. We will leverage data generated as part of past and ongoing studies in the Michigan Polybrominated Biphenyl Cohort and characterize genetic and epigenetic variation in 2 PBB-exposed cohorts, a discovery cohort of 500 subjects exposed through living on or eating food from contaminated farms and a replication cohort of 200 subjects exposed through work at the Michigan Chemical Company that produced PBBs. This research will produce the largest and most comprehensive genetic dataset in subjects exposed to PBBs. We anticipate that this study will provide insight into how genetic variants and the environment interact in relation to PBB exposure and its health effects. We also anticipate the results of this study will be informative for studies of BFRs and other endocrine disrupting compounds with similar chemical properties.

描述（由适用提供）：人类处于前所未有的水平上的化学物质，例如损坏的阻燃剂（BFR），并且各种各样的健康影响归因于这种暴露。但是，将暴露与其后果联系起来的生物学机制尚不清楚。 1970年代的一次工业事故暴露于密歇根州的4000多人身上，向多溴二苯基（PBB）暴露，BFR仍然证明了这些人及其子女的健康影响。由于自暴露以来已经定期评估该人群，因此是一个理想的群体，可以在其中检查有助于易感性，脆弱性和健康影响的分子机制。 The project goals are to: 1) identify the genetic variants that associate with the rate of PBB elimination over time, 2) identify epigenetic patterns that associate with PBB exposure, 3) integrated genetic and epigenetic datasets and identify complex gene-environment relationships in PBB exposed individuals and 4) evaluate the contribution PBB-associated genetic and epigenetic factors to endocrine-related consequences of exposure.我们将利用在密歇根州多溴二手基因组中产生的过去和正在进行的研究的一部分，并表征了2个暴露的队列中的遗传和表观差异，这是500名通过污染农场的食物或食物中的食物而遭受200名受试者以及由200个受试者进行了20000名因化学企业而遭受化学coperion compance coption coption press nicrigigigigigigigigigigigigigigigigigigigigigigigigigigigigigigigigigigigigigigigigi company coptive coply的发现。这项研究将产生暴露于PBB的受试者中最大，最全面的遗传数据集。我们预计，这项研究将提供有关遗传变异和环境如何相对于PBB暴露及其健康影响的洞察力。我们还期望这项研究的结果对于BFR和其他具有相似化学特性的化合物的研究将是有益的。