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: 8065487
• 负责人: Harvey Checkoway
• 金额: $ 29.92万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-04-20 至 2014-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8065487
• 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; 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 对 UW SBRP 来说是一个新项目，它是一项流行病学调查，旨在研究金属作为 专业焊工帕金森病 (PS) 风险、严重程度和进展的决定因素。 先前的流行病学和实验研究已经证明，两者之间存在非常合理的联系。 锰 (Mn) 和其他金属，单独或组合，以及 PS。研究人群包括 875 名威斯康星州造船厂焊工（775 名在职人员，100 名退休人员）和 200 名非暴露造船厂 之前没有参加过 NEIHS 资助的 R01 项目（ES013743； PI：B. Racette；共同研究者：H. Checkoway、N. Seixas）。这项拟议研究的新特点将 细化暴露评估以生成定量的金属特定水平，并重复 PS相关运动功能纵向变化的神经学检查。科学目标 该项目的目的是： 1) 估计锰和其他金属暴露与 PS 风险之间的剂量反应关系 和严重程度； 2) 检验这些金属暴露与 PS 进展相关的假设； 3） 确定项目 3（张博士）中表征的 PS 蛋白质组生物标志物的预测关系， PS 风险、严重程度和进展； 4）用PS测试Mn和其他金属的剂量反应关系 蛋白质组生物标志物概况作为临床前疾病的指标。为了实现这些目标，我们将执行 运动功能的重复标准化神经学检查（统一帕金森病评定量表 运动第 3 部分 [UPDRS3]) 尽可能多的学习科目的入学考试后 3 年 已入学（约 75%）。此外，与项目 3 合作，我们将收集血浆样本用于分析 已针对选定的 150 名受试者样本验证其与 PS 密切相关的蛋白质组学 根据基线 UPDRS3（“正常”、临界 PS、可能/确定 PS）。潜在数据 重要的混杂因素，特别是吸烟和农药暴露，将通过以下方式获得 调查问卷。该项目在量化金属对神经系统影响的程度方面具有巨大潜力， 是广泛存在的环境污染物，因此可能有助于疾病预防策略。