Abstract
Objective: To determine and compare DNA methylation patterns between patients with Parkinson’s disease (PD) and age- and sex-similar matched non-PD controls. Background: Epigenetic regulation is one of the major mechanisms for an organism to respond to the environment through changes in gene expression and has been implicated in numerous disease processes. We would like to examine epigenetic modification patterns that may predispose or protect against PD. Methods: Frozen tissue samples of the human cerebral cortex from 12 PD patients and 12 subjects without PD pathology were obtained. Genome-wide DNA methylation profiling was performed using the Illumina HumanMethylation450 BeadChip array. Differential methylation was defined as a mean methylation level difference (delta β) of at least 0.20 (Δβ ≥ 0.20). Methylation regions with an absolute delta β value ≥ 0.20 were selected for further gene function studies. Results: We identified 2795 differentially methylated CpG sites in the frontal cortex of PD cases with a detection p-value of ≤ 0.01 and 328 differentially methylated CpG sites with a detection p-value of ≤ 0.001. A pattern of robust hypermethylation of synphilin-1, α-synuclein-interacting protein (SNCAIP) gene was found in the brain of PD cases (p = 4.93 × 10−7 and delta β = 0.60). Conclusion: Our findings support a link between SNCAIP methylation and PD risk. Hypomethylation of SNCAIP may function to protect against PD. The current results may suggest that the methylation status of SNCAIP could be useful as a marker in PD diagnosis and treatment and warrants further investigation.
Highlights
The etiopathogenesis of neurodegenerative disorders including Parkinson’s disease (PD) is not clear but interactions between genes and environmental pathogens seem to play a major role in PD [1].Multiple genes have been discovered that contribute to the development of PD but still the majority of the sporadic PD patients do not carry a specific identified gene [2,3]
Another possibility would be that there exist certain ubiquitous environmental factors that can cause PD in all people, but that the majority of the population carries one, or most likely multiple, unknown genes that protect against the development of the disease [5]
A pattern of robust hypermethylation of synphilin-1, α-synuclein-interacting protein (SNCAIP) gene was found in the brain of PD cases (p = 4.93 × 10−7 and delta β = 0.60)
Summary
The etiopathogenesis of neurodegenerative disorders including Parkinson’s disease (PD) is not clear but interactions between genes and environmental pathogens seem to play a major role in PD [1].Multiple genes have been discovered that contribute to the development of PD but still the majority of the sporadic PD patients do not carry a specific identified gene [2,3]. The etiopathogenesis of neurodegenerative disorders including Parkinson’s disease (PD) is not clear but interactions between genes and environmental pathogens seem to play a major role in PD [1]. Brain Sci. 2017, 7, 74; doi:10.3390/brainsci7070074 www.mdpi.com/journal/brainsci. Brain Sci. 2017, 7, 74 localized brain regions, leading to PD [4]. Gene–environment interactions seem to play a major role in the initiation of the PD disease process. Another possibility would be that there exist certain ubiquitous environmental factors that can cause PD in all people, but that the majority of the population carries one, or most likely multiple, unknown genes that protect against the development of the disease [5]
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