The goal is to identify the factors that affect age at onset of PD, so that effective strategies can be devised to delay the onset.
The Specific Aim of this study is to test for a genetic influence on onset age of PD. Three candidate loci will be examined: Apolipoprotein E (APOE), the human leukocyte antigen A (HLA-A), and cytochrome P450 (CYP2D6). APOE and HLA-A modulate onset age of Alzheimer disease (AD), and may have a similar effect on onset age of PD. The known function of APOE in neuronal repair, and of HLA-A in immune and inflammatory response, suggest that they may play a general role in neurodegeneration. Identification of genes that predispose to more than one neurodegenerative disorder would help understanding of key mechanisms of neurodegeneration. CYP2D6 is involved in metabolism of environmental toxins, and the mutant B allele is reportedly a risk factor for PD and may be associated with earlier disease onset. The subjects will include 600 unrelated patients with diagnosis of idiopathic PD, and 311 relatives from 66 familial PD kindreds. Every subject and key family member will be evaluated by a neurologist for cognitive and motor function, and followed to death for brain autopsy. A blood sample will be obtained for genotyping (by PCR), DNA banking and establishing immortalized cell lines. Genotype-specific age at onset will be tested using Kaplan-Meier/log-rank method to compare the distributions of onset ages, and student t test to compare the mean onset ages. This study utilizes the resources and the long-standing collaboration between AD and PD centers in Portland and Seattle.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS036960-03
Application #
6165527
Study Section
Epidemiology and Disease Control Subcommittee 2 (EDC)
Program Officer
Oliver, Eugene J
Project Start
1998-03-01
Project End
2002-03-31
Budget Start
2000-03-01
Budget End
2002-03-31
Support Year
3
Fiscal Year
2000
Total Cost
$181,768
Indirect Cost
Name
Oregon Health and Science University
Department
Genetics
Type
Schools of Medicine
DUNS #
009584210
City
Portland
State
OR
Country
United States
Zip Code
97239
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