Parent Title:
Effects-Related Biomarkers of Environmental Neurotoxic Exposures
Grant Number:
Principal Investigator:
Checkoway, Harvey
Institution:
University of Washington
Most Recent Award Year:
2009
Lifestage of Participants:
Exposure:
Adulthood (18+ years)
Assessment:
Adulthood (18+ years)
Exposures:
Metals:
Aluminum; Chromium; Copper; Iron; Lead; Manganese
Mixtures:
Health Outcomes:
Neurological / Cognitive Outcomes:
Parkinsonism
Biological Sample:
Plasma
Other Participant Data:
Neurological exams of motor function using Unified Parkinson's Disease Rating Scale Motor Subsection 3 [UPDRS3]; Questionnaire to obtain data on cigarette smoking and pesticide exposure as cofounders
Abstract:
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.
ExpandCollapse Abstract
Related NIEHS-Funded Study Populations
Parkinsonism and Metal Exposures Among Welders
Principal Investigator:
Racette, Brad; Checkoway, Harvey
| Study Population Page Study Population c116
Institution:
Washington University
Location:
Wisconsin
Number of Participants::
875 welders and 200 controls
Brief Description::
This is an occupational cohort study examining how exposure to manganese and other metals affects the risk, severity, and progression of Parkinsonism and Parkinson’s disease among professional welders. Since 2005, the study has enrolled 875 Wisconsin shipyard welders (775 actively employed, 100 retired) and 200 non-exposed shipyard workers.