Investigators have used 2 approaches to probe the cause of Parkinson's disease (PD):epidemiologic methods to identify putative risk factors; and both genetic-epidemiologic and biochemical techniques to detect genes that might confer genetic susceptibility to PD. However, there has been no definitive cause identified as yet, and there is evidence to imply that both environmental and genetic factors may be involved. In this investigation we propose to examine a number of putative antecedent environmental risk factors and their relationship to one putative marker of genetic susceptibility to PD. Using a case-control design we will compare the frequency of specific dietary, environmental and genetic risk factors in patients with PD and the controls all of whom will be 65 years of age or older and residing in the community of Washington Heights-Inwood. Recently diagnosed patients with PD without evidence of dementia and healthy elderly controls, free of PD and dementia, identified during the funding period of another project will form the subject groups for this investigation. All cases will have met rigorous research criteria for the diagnosis of PD and have been diagnosed within the last 5 years, and controls will be selected from a random sample of elderly from the same community (participating in another study) by frequency matching for age (by 2 years) ethnic group and gender. We will conduct standardized interviews to obtain a detailed dietary information and to ascertain exposure data regarding putative risk factors. Serum ferritin will be determined as a measure of body iron stores and we will also collect blood to extract DNA in order to determine the frequency of various CYP2D6 debrisoquine hydroxylase gene alleles in both cases and controls. We will examine CYP2D6 locus-environment interaction by examining the associations between the presence of CYP2D6 polymorphisms and various dietary or environmental risk factors. We intend to investigate 2 major hypotheses: First, that regular consumption of foods high in dietary iron, in elderly individuals with normal or decreased body stores of iron, will b associated with PD. Second, that a specific CYP2D6 allele will be a marker of genetic susceptibility to PD, and that exposure to putative environmental risk factors may further increase the risk of PD in these genetically susceptible individuals.
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