Parkinson's Diseases Susceptibility Genes and Pesticides

帕金森病易感基因和农药

• 批准号: 8391721
• 负责人: Beate R Ritz
• 金额: $ 63.06万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-02-01 至 2015-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8391721
• 关键词: Address; Age; Aging; Agriculture; Air; Alzheimer' s Disease; Behavioral; Boston; Brain Diseases; Caffeine; California; Case-Control Studies; Clinical Trials; Communities; Complex; Computer Simulation; County; DNA; Data; Disease; Disease susceptibility; Enrollment; Environment; Environmental Exposure; Environmental Wind; Exposure to; Farming environment; Funding; Future; Gene Mutation; Genes; Genetic; Genetic Variation; Geographic Information Systems; Grant; HTRA2 gene; Haplotypes; Height; Home environment; Human; Inherited; Interview; Investigation; Knowledge; LRRK2 gene; Laws; Life Style; Maps; Measurement; Medical History; Modeling; Movement Disorders; Names; National Institute of Environmental Health Sciences; Neurologist; Neurons; Occupational; PARK2 gene; PARK6 gene; PARK8 gene; Parkinson Disease; Participant; Patients; Pesticides; Phenotype; Pilot Projects; Population; Population Control; Population Study; Predisposition; Prevention; Public Policy; Quality of life; Recruitment Activity; Registries; Regulation; Reporting; Research; Resources; Risk; Risk Factors; Rural; Sample Size; Sampling; Smoking; Soil; Specialist; Speed; Subgroup; Susceptibility Gene; Testing; Therapeutic; Time; Toxic Environmental Substances; Toxin; UCHL1 gene; Universities; Variant; Vulnerable Populations; Water; Water Pollution; Work; alpha synuclein; base; cost; data sharing; disability; disease diagnosis; disorder risk; gene interaction; genetic variant; improved; innovation; land use; novel; parkin gene/protein; parkinson' s disease registry; pesticide exposure; pesticide interaction; public health relevance; rural area; therapeutic development; tool; toxicant interaction; validation studies

DESCRIPTION (provided by applicant): We propose expanding our existing Parkinson's disease, Environment and Genes (PEG) study population to further investigate the contributions of specific agricultural pesticides alone and in combination with biologically relevant genes that increase susceptibility to Parkinson's disease (PD). With prior funding, we have already enrolled 363 movement disorder specialist-confirmed idiopathic PD patients and, by the end of 2010, have enrolled 910 population controls from a heavily pesticide exposed population in three rural counties of California's Central Valley. All PEG study participants provide a biologic sample, complete a risk factor interview that includes detailed pesticide/farm work exposure assessments, and provide lifetime residential and occupational addresses that are combined with California state mandated commercial pesticide use reports in our sophisticated geographic information system (GIS) computer model to estimate ambient pesticide exposure over time. Our specific aims in this application are (1) Establish the largest case-control study of well characterized incident Parkinson's disease in the US with unprecedented pesticide exposure assessment by recruiting 500 additional movement disorder specialist-confirmed incident cases of PD utilizing the California PD Registry - a unique and time-limited resource for PD research given that the financial situation of the state of California jeopardizes future state funding to continue this effort and the 2,600 patients already identified are aging and progressing rapidly with regard to disease state; (2) Create a novel, comprehensive tool to assess pesticide exposures by incorporating data on wind speed, direction, and atmospheric mixing heights, farm boundaries, and soil composition and groundwater flow; and expand and validate our existing GIS-based computer model of pesticide exposure by incorporating occupational addresses, in addition to residential addresses, to estimate exposure to commercial pesticides and validating our model using Dept of Pesticide Regulation and CA Air Resource Board water and air measurements; and (3) Investigate novel gene-pesticide interactions for recognized PD risk genes (PARK1/PARK4 SNCA, PARK2 parkin, PARK5 UCHL1, PARK6 PINK, PARK8 LRRK2, and PARK13 HTRA2). While the PEG study has provided important and groundbreaking first results on pesticide and pesticide-gene interactions in PD in humans, this application provides the opportunity to increase our sample size and therefore our statistical power to evaluate the impact of less commonly used pesticides, combinations of pesticides, less frequent genetic mutations, and GxE interactions with one of the best pesticide exposure assessment models in a well defined and extensively phenotyped case population. Improving our understanding of environmental toxins, the genetic variation, and their impact on idiopathic PD will improve prevention efforts, advance therapeutic developments, and inform public policy on pesticide regulation.

描述（由申请人提供）：我们建议扩大现有的帕金森氏病，环境和基因（PEG）研究人群，以进一步研究单独的特定农用农药的贡献，并与生物学上相关的基因相结合，以增加对帕金森氏病（PD）的易感性。有了先前的资金，我们已经招募了363个运动障碍专家，并确认了特发性PD患者，到2010年底，在加利福尼亚州中部三个农村县的农药暴露的人口中，已经招募了910个人口控制。所有PEG研究参与者都提供生物学样本，完成包括详细农药/农场工作暴露评估的危险因素访谈，并提供终生的住宅和职业地址，这些住宅和职业地址与加利福尼亚州强制性的商业农药使用报告相结合，在我们复杂的地理信息系统（GIS）计算机模型中，以估算环境诸如环境的曝光。我们在此应用中的具体目的是（1）建立对帕金森氏病的良好特征性事件的最大病例对照研究，通过招募500个其他运动障碍专家确认的PD的案例，通过招募500个其他运动障碍的事件，利用加利福尼亚州PD登记率的PD - 延长了一项独特的和时间限制的PD研究，该案件的PD案件是普通的，这是一项独特的和限时的研究。在疾病状态下，已经确定的2600名患者正在衰老和进展。 （2）创建一种新颖的，全面的工具，通过合并有关风速，方向和大气混合高度，农场边界以及土壤组成和地下水流的数据来评估农药暴露；除了将职业地址（除住宅地址）合并，以估计接触商业农药，并使用农药调节部和CA空气资源委员会的水和空气测量，并通过纳入职业地址（除住宅地址）来扩展和验证我们现有的基于GIS的农药暴露计算机模型； （3）研究公认的PD风险基因的新型基因农药相互作用（PARK1/PARK4 SNCA，PARK2 PARKIN，PARK5 UCHL1，PARK6 UCHL1，PARK6 PINK，PARK8 LRRK2和PARK13 HTRA2）。 While the PEG study has provided important and groundbreaking first results on pesticide and pesticide-gene interactions in PD in humans, this application provides the opportunity to increase our sample size and therefore our statistical power to evaluate the impact of less commonly used pesticides, combinations of pesticides, less frequent genetic mutations, and GxE interactions with one of the best pesticide exposure assessment models in a well defined and extensively phenotyped case population.提高我们对环境毒素的理解，遗传变异及其对特发性PD的影响将改善预防努力，提高治疗发展，并为农药调节提供公共政策。