Journal
MOVEMENT DISORDERS
Volume 30, Issue 4, Pages 577-580Publisher
WILEY
DOI: 10.1002/mds.26073
Keywords
Parkinson's disease; methylation; SNCA; quantitative-trait locus; epigenetics
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Funding
- Health Region South-East, Norway
- Research Council of Norway
- Norwegian Parkinson Research Fund
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BackgroundGenome-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. MethodsWe 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). ResultsPatients 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 x 10(-5)) and brain (P=0.023). ConclusionsOur 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. (c) 2014 International Parkinson and Movement Disorder Society
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