Grantee Research Project Results
2000 Progress Report: Genetic Polymorphisms in Xenobiotic Metabolism as Susceptibility Factors for Parkinson's Disease
EPA Grant Number: R827017Title: Genetic Polymorphisms in Xenobiotic Metabolism as Susceptibility Factors for Parkinson's Disease
Investigators: Chan, Piu
Institution: Parkinson's Institute
EPA Project Officer: Hahn, Intaek
Project Period: October 1, 1998 through September 30, 2001 (Extended to September 30, 2002)
Project Period Covered by this Report: October 1, 1999 through September 30, 2000
Project Amount: $554,324
RFA: Interindividual Variation in Human Susceptibility to Environmentally-caused Disease (1998) RFA Text | Recipients Lists
Research Category: Human Health
Objective:
The primary objective of this project is to investigate genetic polymorphisms of two xenobiotic enzymes that may increase the susceptibility to Parkinson's disease (PD) by impairing the ability to metabolize exogenous and/or endogenous toxicants. Specifically, this project involves the following tasks: (1) extracting DNA from dry blood spot on paper cards that already have collected from Chinese PD cases and controls; (2) determining the genotypes for the GSTM1 and GSTT1 null alleles and the CYP2D6*2 (L) and CYP2D6*10 (J) alleles; and (3) examining the individual and joint effects of these polymorphisms as they contribute to the risk of developing PD.Progress Summary:
In Year 1 of the project (10/98-9/99), DNA from 400 subjects has been extracted, and both the GSTM1 and GSTT1 null alleles have been performed in 190 subjects. In addition, certain number of PD subjects has been either re-examined or reviewed with videotapes by a movement disorder specialist. These processes will ensure the quality of the diagnosis made by the Chinese neurologists.In the second year of the project, we finished the DNA extraction from all 570 subjects collected. We have finished the genotyping of GSTM1 and GSTT1 null alleles in all PD cases and controls. In addition, we have determined the genotypes of CYP2D6*2 and CYP2D6*10 alleles in about 300 and 200 subjects, respectively. A database already has been set up and obtained genetic and epidemiological data have been entered into the database.
Future Activities:
It is expected that genotyping of CYP2D6*2 and CYP2D6*10 alleles in all subjects will be completed by February 2001. Then, the subject's code will be opened. Statistical analyses will be carried out to determine the association between the genetic polymorphic alleles and risk for PD either individually or in combination. Possible gene-environment interaction in the development of PD also will be studied. These activities are as planned in the original proposal and no changes are expected to be made in the next project period.Supplemental Keywords:
vulnerability, sensitive population, genetic predisposition, susceptibility., Health, Scientific Discipline, Health Risk Assessment, Risk Assessments, Biology, Biochemistry, Disease & Cumulative Effects, Toxicology, enzyme systems, xenobiotics, biological markers, cytochrome P450, human exposure, genetic polymorphisms, neurotoxicity, susceptibility, genotypes, polymerase chain reaction, gene-environment interactionRelevant Websites:
http://www.parkinsonsinstitute.org
Progress and Final Reports:
Original AbstractThe perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Conclusions drawn by the principal investigators have not been reviewed by the Agency.