Superfund Research Program
Environmental and Genetic Risk Factors for Parkinson's Disease
Project Leader: Harvey Checkoway (University of California-San Diego)
Grant Number: P42ES004696
Funding Period: 1995 - 2009
Final Progress Reports
Project investigators continue to enroll Parkinson's disease (PD) cases and controls from the membership of Group Health Cooperative of Puget Sound, Washington. To date, data has been collected on 201 PD cases and 304 controls. Questionnaires eliciting data on environmental exposures, medical history, medication use, smoking, and diet have been administered. Researchers continue to observe the predictable inverse relation between cigarette smoking and PD risk. Analyses of occupational exposures suggest positive risk gradients with long-term employment in vegetable farming, sawmill work, and aerospace assembly. Further analyses with respect to specific environmental agents, especially pesticides, metals, and solvents, are in progress. The researchers have assayed genetic variants of genes for: cytochrome P450 enzymes (2D6, 1A1, 2E1), monoamine oxidases (MAO) A and B, dopamine D2 receptor, superoxide dismutases (SOD1, SOD2), and the ND1 subunit of mitochondrial Complex I. Elevated risks associated with the G allele of the MAO-B intron 13 persist, as does the interaction with cigarette smoking. Investigators found a roughly 2-fold excess in males for the T4216C mutant form of the ND1 Complex I gene in males, but no relation in females. No associations with PD were observed for either the EcoRV genetic polymorphism of MAO-A or the TaqIA and TaqIB variants of the dopamine D2 receptor gene. Thus far, no significant associations with variants of the cytochrome P450 genes have been detected, although additional subject accrual will permit assessments of gene/environment interactions. Ongoing work involves detection of coding and promoter region polymorphisms of MAO-B, and exploration of genetic variants of the glutathione S-transferases (GST), with particular emphasis on novel mutations in the GSTM2 gene. This latter work will be accompanied by studies of the enzymatic functional significance of these gene variants.