Parkinson's disease correlates with promoter methylation in the α-synuclein gene
Lasse Pihlstrøm1, Victoria Berge, Aina Rengmark
1Department of Neurology, Oslo University Hospital, Oslo, Norway.
Background:
Genome-wide association studies have demonstrated association between SNCA variability and susceptibility to Parkinson's disease, but causal mechanisms are unclear. We hypothesized that risk variants affect methylation of a putative promoter in SNCA intron 1, previously highlighted in epigenetic studies of Parkinson's disease.
Methods:
We analyzed sample sets from blood (n = 72) and cerebral cortex (n = 24) in Parkinson's disease patients and healthy controls. We genotyped SNCA single-nucleotide polymorphisms, examined messenger RNA (mRNA) expression and assessed intron 1 methylation levels by methylation-sensitive restriction enzyme digestion and quantitative polymerase chain reaction (PCR).
Results:
Patients showed significant hypomethylation as compared with controls in the blood sample set. In addition, rs3756063 was associated with SNCA methylation level in both blood (P = 5.9 × 10(-5)) and brain (P = 0.023).
Conclusions:
Our findings support a link between SNCA variability, promoter methylation, and Parkinson's disease risk and indicate that methylation patterns in brain are mirrored in the blood. SNCA methylation warrants further investigation as a potential biomarker.
Related Concept Videos
Parkinson Disease ll: Pathophysiology
Parkinson Disease l: Introduction
Parkinson's Disease: Overview
Parkinson's Disease: Treatment
Parkinson's Disease is primarily a result of the loss of dopaminergic neurons in the substantia nigra pars compacta. The cornerstone of...
Neural Regulation
Alzheimer Disease l: Introduction


