Parkinson's disease correlates with promoter methylation in the α-synuclein gene.
2015
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 5 72) and cerebral cortex (n 5 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 5.9 3 10 25 ) and brain (P 5 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. V C 2014 International Parkinson and Movement Disorder Society
Keywords:
- Correction
- Source
- Cite
- Save
- Machine Reading By IdeaReader
35
References
68
Citations
NaN
KQI