Genetic and Environmental Factors in Parkinson's Disease
Edmond J. Safra Global Genetics Consortia, 2004
Epidemiologic studies in recent years have convincingly demonstrated that cigarette smoking and coffee drinking are less common among individuals who have developed Parkinson's disease (PD) than control subjects, incidating that these factors may prevent or delay the onset of PD. Despite the consistency of these findings across studies, there has been very little research to investigate the biological reasons for the apparent protective effect of cigarette smoke and caffeine. As an initial effort of the Consortium for the Study of Genetic and Environmental Factors in Parkinson's Disease, we will investigate how the risk of developing PD varies according to tobacco and caffeine intake, and whether certain genetic factors influence the protective effect of these agents. Scientists in the consortium have selected ten candidate genes that may help to explain the apparent beneficial effects of nicotine and caffeine on the pathogenesis of Parkinson's disease. The candidate genes of interest are those that involved in the body's metabolism of chemical constituents of tobacco and caffeine, as well as those that are important for regulating dopamine, the neurotransmitter that is depleted in Parkinson's disease. The consortium project will use DNA samples and risk factor data that were obtained in seven previous epidemiologic studies, with a total of 1700 PD patients and 2100 age- and gender-matched control subjects. The consortium will benefit from have a large number of PD cases in several subgroups of interest, including individuals with a younger age at PD diagnosis, and members of racial or ethnic subgroups that have not received as much investigation (e.g., Hispanics, Asians and African Americans). By combining a laboratory-based study of the candidate genes with detailed information from PD cases and controls regarding cigarette smoking and caffeine consumption, we hope to understand why these factors reduce the risk of Parkinson's disease. Ultimately, if the reasons for the protective ffect of tobacco and caffeine are understood, treatments could be developed to inhibit the development of PD or reduce the progression of the disease once it has begun.
The team obtained epidemiologic data and DNA from a total of 3,180 subjects, including 1,300 PD cases and 1,700 gender- and age-matched control subjects. The study benefitted from having a greater number of PD cases in several subgroups of interest, including PD patients under 60 years of age (497 cases) and members of racial/ethnic subgroups including non-Hispanic Caucasians (1,035 cases, 1,279 controls), Hispanics (141 cases, 164 controls), Asians (120 cases, 226 controls), and African Americans (29 cases, 66 controls). A large number of candidate genes were under study (14 candidate genes and 54 single-nucleotide polymorphisms, or SNPs), requiring intensive statistical analysis.
Preparation of manuscripts for publication is currently under way.
Associate Professor & Chief, Division of Epidemiology at Stanford University
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