Project 2: Parkinsonism and Metal Exposures Among Welders

项目 2：焊工的帕金森症和金属暴露

• 批准号: 8254485
• 负责人: Harvey Checkoway
• 金额: $ 26.85万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-04-07 至 2014-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8254485
• 关键词: Aluminum; Biological Assay; Biological Markers; Chromium; Collaborations; Copper; Data; Disease; Dose; Early Diagnosis; Enrollment; Environmental Pollution; Epidemiologic Studies; Epidemiology; Exposure to; Funding; Investigation; Iron; Knowledge; Lead; Link; Manganese; Metal exposure; Metals; Motor; National Institute of Environmental Health Sciences; Neurologic; Neurologic Examination; Occupational Groups; Parkinson Disease; Parkinsonian Disorders; Plasma; Population; Population Study; Predisposition; Prevalence; Prevention program; Prevention strategy; Proteomics; Questionnaires; Recording of previous events; Research Personnel; Risk; Risk Assessment; Role; Sampling; Severities; Signs and Symptoms; Study Subject; Testing; Welding; Wisconsin; cigarette smoking; cohort; disorder prevention; gene environment interaction; neurotoxic; pesticide exposure; pre-clinical; research study; response; toxicant

Project 2, which will be new to the UW SBRP, is an epidemiologic investigation of the roles of metals as determinants of the risk, severity, and progression of parkinsonism (PS) among professional welders. Previous epidemiologic and experimental research has demonstrated very plausible links between manganese (Mn) and other metals, individually and in combination, and PS. The study population includes 875 Wisconsin shipyard welders (775 actively employed, 100 retired) and 200 non-exposed shipyard workers with no welding exposure history previously enrolled in an ongoing NEIHS-funded R01 (ES013743; PI: B. Racette; Co-investigators: H. Checkoway, N. Seixas). The new features of this proposed study will be the refinement of exposure assessment to generate quantitative metal-specific levels, and repeated neurological examinations of longitudinal change of PS-related motor function. The scientific objectives of the project are to: 1) estimate dose-response relations between Mn and other metal exposures and PS risk and severity; 2) test the hypothesis that these metal exposures are associated with PS progression; 3) determine the predictive relations of PS proteomic biomarkers, characterized in Project 3 (Dr. Zhang), with PS risk, severity, and progression; 4) test dose-response relations for Mn and other metals with PS proteomic biomarker profiles as indicators of preclinical disease. To achieve these objects, we will perform repeated standardized neurological exams of motor function (Unified Parkinson's Disease Rating Scale Motor Subsection 3 [UPDRS3]) 3 years after enrollment exams for as many study subjects as can be enrolled (~75%). Addionally, in collaboration with Project 3, we will collect plasma samples for assays of proteomics that have been validated as strongly associated with PS for a sample of 150 subjects selected according to baseline UPDRS3 ('normal', borderline PS, probable/definite PS). Data on potentially important confounding factors, especially cigarette smoking and pesticide exposure, will be obtained by questionnaire. This project has great potential to quantify the extent of neurological effects of metals, which are widespread environmental contaminants, and thus could contribute to disease prevention strategies.

项目2将是UW SBRP的新事物，是对金属作为专业焊工中帕金森主义（PS）风险，严重性和进展的决定因素的流行病学研究。以前的流行病学和实验研究表明，锰（MN）与其他金属之间的单独，组合以及PS之间的联系非常合理。研究人群包括875个威斯康星州造船厂焊工（775名积极使用，100名退休）和200个非暴露造船厂 没有焊接历史记录的工人先前参加了正在进行的Neihs资助的R01（ES013743; PI：B。Racette; cotette;共同投资者：H。Checkoway，N。Seixas）。这项拟议的研究的新特征将是对暴露评估的改进，以产生定量金属特异性水平，并重复进行与PS相关运动功能的纵向变化的神经系统检查。该项目的科学目标是：1）估计MN与其他金属暴露与PS风险和严重性之间的剂量反应关系； 2）检验这些金属暴露与PS进展相关的假设； 3）确定PS蛋白质组学生物标志物的预测关系，其特征在项目3（Zhang博士）中，具有PS风险，严重性和进展； 4）MN和其他具有PS蛋白质组学生物标志物谱的MN和其他金属的测试剂量反应关系是临床前疾病的指标。为了实现这些对象，我们将在入学率考试后3年进行运动功能的重复标准化神经检查（统一的帕金森氏病评级量表运动量表第3 [UPDRS3]）。此外，我们将与项目3合作，我们将收集血浆样品，以进行蛋白质组学的测定，这些蛋白质组学与PS相关的蛋白质组学对150个受试者的样本（根据基线UPDRS3（“正常”），边界PS，可能/确定的PS）进行了验证。问卷将获得有关潜在重要混杂因素，尤其是吸烟和农药暴露的数据。该项目具有巨大的潜力，可以量化金属的神经系统作用的程度，金属是广泛的环境污染物，因此可能有助于预防疾病的策略。