The proposed epidemiologic study will evaluate the contribution of environmental and genetic factors to the etiology of Parkinson's disease (PD). Of particular interest are substances that are similar in chemical structure or mechanism of action to established toxicants for secondary parkinsonism, a disorder that shares some clinical and pathologic features with idiopathic PD. The focus will be on Settings where high dose or chronic exposure may have taken place, specifically, the agricultural environment, industrial settings, diet and the home. A putative biomarker of genetic susceptibility of impaired toxicant metabolism, the CYP2D6 gene that encodes for the P450 enzyme debrisoquine hydroxylase, will be measured. This is a common enzymatic pathway for the metabolism of many of the neurotoxicants under study. The role of putative protective factors (i.e. dietary antioxidants, cigarette smoking, skin pigmentation) that may minimize the toxicity of exogenous exposures will also be evaluated. We propose to conduct a case-control study of incident PD cases identified within the Kaiser Permanente Medical Care Program (KPMCP) of Northern California. Over a three-year period, physician referrals and computerized records will be used to maximize the ascertainment of newly diagnosed cases of PD. Approximately 600 cases will be enrolled, and compared to an equal number of control subjects selected from computerized KPMCP membership files (individually matched to cases by gender, age, KPMCP service area). Study information will be collected by structured interview and will include: demographic characteristics, residence history, lifetime occupational history, hobbies, home exposures, illicit and prescription drug use, family history, cigarette smoking, and dietary habits. Blood samples will be drawn for CYP2D6 genotyping. Conditional logistic regression will be used to provide odds ratio estimates for the exposures of interest. The collection of detailed information regarding the duration and timing of environmental exposures will enable the evaluation of dose-response trends and the estimation of latent periods between putative exposure and the development of Parkinson's disease. It is hoped that the proposed study will advance knowledge of potential neurotoxic and genetic risk factors for PD in a racially and geographically diverse population.
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