Abstract
Objective: To investigate whether there are significant differences in DNA methylation between Parkinson Disease (PD) cases and controls in three brain regions affected in PD. Background: Environmental exposures have been shown to affect the risk of PD. Because DNA methylation states are known to be affected by environment causes, we investigated whether this could be a contributor to PD. As DNA methylation is known to be both tissue and tissue-region specific, we used three regions for the analysis. The dorsal motor nucleus of the vagus (DMV), recognized to be one of the earliest regions affected in PD, the substantia nigra (SN), the primary area of neurodegeneration, and the cingulate gyrus (CG), which is affected in the later stages of PD. Design/Methods: DNA methylation patterns with PD were investigated by performing a genome-wide screen of DNA methylation using the Illumina 450 methylation beadchip on 12 autopsy-confirmed PD and 11 autopsy-confirmed controls. Results: 9,621 CpG sites were found to be differentially methylated between PD and controls at FDR Conclusions: The DMV is a nucleus with potential environmental exposure via the vagus nerve and the gastrointestinal tract. Further, it has repeatedly been found to be an area demonstrating the earliest PD pathology. Our data suggest that methylation changes occur in the DMV and are affecting genes involved in neurotransmission and neurodegenerative pathways. This supports methylation as a likely factor in early PD. Study Supported by: NIH/NINDS P50NS071674 Disclosure: Dr. Vance has received personal compensation in an editorial capacity for Neurology Genetics. Dr. Vance9s institution has received royalty payments from Athena Diagnostics. Dr. Sivasankaran has nothing to disclose. Dr. Wang has nothing to disclose. Dr. Mehta has nothing to disclose. Dr. Davis has nothing to disclose. Dr. Belle has nothing to disclose. Dr. Dykxhoorn has nothing to disclose. Dr. Beecham has nothing to disclose. Dr. Martin has nothing to disclose. Dr. Mash has nothing to disclose. Dr. Scott has nothing to disclose. Dr. young has nothing to disclose.