UNIVERSITY OF MIAMI
There is overwhelming evidence for a central role of mitochondrial dysfunction in Parkinson's Disease. This project is based upon our report of a significant association of the mitochondrial J and K haplogroups with Parkinson Disease (PD). In the parent grant we have performed a genome wide expression study on PD patient fibroblast lines carrying different mitochondrial haplogroups. The most robust differential gene expression came from the Glutathione S transferase theta 1 (GSTT1) gene. GSTT1 encodes a key enzyme that metabolizes compounds in cigarettes; yet, smoking has a protective effect on PD risk. Interestingly, we recently reported another member of this gene family (GSTO1) as a modifier gene for age-at-onset (AAO) of both PD and Alzheimer’s disease. Finally, our recent GWAS analysis showed significant association of copy number variants (CNVs) in GSTT1 with PD. The administrative supplements will allow us to continue our current studies in this project, but specifically confirm these exciting findings in an independent PD dataset.