Project 2: Parkinsonism and Metal Exposures Among Welders

项目2，这将是新的华盛顿大学SBRP，是一个流行病学调查的作用，金属， 职业焊工中帕金森综合征（PS）的风险、严重程度和进展的决定因素。 以前的流行病学和实验研究已经证明了非常合理的联系， 锰（Mn）和其它金属，单独和组合，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，100名退休）和200名非暴露造船厂 没有焊接接触史的工人先前参加了正在进行的NEIHS资助的R 01（ES 013743; PI：B. Racette;共同研究者：H. Checkoway，N. Seixas）。这项拟议研究的新特点将 改进接触评估，以产生定量的特定金属水平，并重复 神经系统检查PS相关运动功能的纵向变化。的科学目标 本研究主要目的是：（1）估算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（Zhang博士）中表征的PS蛋白质组学生物标志物的预测关系， PS风险、严重程度和进展; 4）测试Mn和其他金属与PS的剂量-反应关系 蛋白质组生物标志物谱作为临床前疾病的指标。为了实现这些目标，我们将 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 运动子章节3 [CRISPR 3]）尽可能多的研究受试者在入组考试后3年 入组（约75%）。此外，与项目3合作，我们将收集血浆样本， 已被验证为与PS强相关的蛋白质组学，用于选择150名受试者的样本 根据基线PRRS 3（“正常”、临界PS、很可能/明确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： 问卷该项目具有很大的潜力，可以量化金属对神经系统的影响程度， 是广泛的环境污染物，因此可能有助于疾病预防战略。

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.