Genetic Polymorphisms in Xenobiotic Metabolism as Susceptibility Factors for Parkinson's Disease

EPA Grant Number: R827017
Title: Genetic Polymorphisms in Xenobiotic Metabolism as Susceptibility Factors for Parkinson's Disease
Investigators: Chan, Piu
Institution: Parkinson's Institute
EPA Project Officer: Fields, Nigel
Project Period: October 1, 1998 through September 30, 2001 (Extended to September 30, 2002)
Project Amount: $554,324
RFA: Interindividual Variation in Human Susceptibility to Environmentally-caused Disease (1998) RFA Text |  Recipients Lists
Research Category: Health Effects , Health

Description:

Parkinson's disease (PD) is suggested to be caused by exposure to exogenous and endogenous neurotoxicants in genetically susceptible individuals. Based on our preliminary findings in North Americans of European descent, we hypothesize that genetic defects of the enzymes cytochrome P450 2D6 (CYP2D6) and glutathione S-transferase (GST) are important genetic susceptibility factors in PD. The primary objective of this study is to further investigate genetic defects of these enzymes that may increase the susceptibility to PD in a second ethnic group. To do this, we will take advantage of blood samples already performed in 15 Chinese research centers.

Approach:

Using polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP) method, the frequency of the CYP2D6 L (arginine296 to cysteine) and J (proline34 to serine) alleles and the null genotype of the class mu GST (GSTM1) and the class theta GST (GSTT1) will be determined in approximately 300 PD cases and 300 controls from a 15-center case-control study in China. We will also examine the individual and joint effects of these mutant CYP2D6 alleles and the null genotypes of GSTM1 and GSTT1 as they contribute to the risk of developing PD.

Expected Results:

We will be able to answer whether or not the genotypes of CYP2D6 L and J alleles and the null GSTM1 and GSTT1 genotypes are individually or jointly associated with an increased risk for PD in the Chinese population. The identification of genetically defective xenobiotic enzymes as risk factors for PD may lead to a more accurate assessment of candidate toxicants, to an early diagnosis of patients, and more importantly the screen for high risk population and the primary prevention for the disease.

Supplemental Keywords:

Risk Assessment, Chemicals; Toxic Substances, Risk Management,, Health, Scientific Discipline, Toxicology, Health Risk Assessment, Risk Assessments, Disease & Cumulative Effects, Biochemistry, Biology, xenobiotics, cytochrome P450, gene-environment interaction, enzyme systems, neurotoxicity, polymerase chain reaction, human exposure, susceptibility, genetic polymorphisms, genotypes, biological markers

Relevant Websites:

http://www.parkinsonsinstitute.org Exit

Progress and Final Reports:

2000 Progress Report