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Parkinson's disease correlates with promoter methylation in the α‐synuclein gene
Author(s) -
Pihlstrøm Lasse,
Berge Victoria,
Rengmark Aina,
Toft Mathias
Publication year - 2015
Publication title -
movement disorders
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.352
H-Index - 198
eISSN - 1531-8257
pISSN - 0885-3185
DOI - 10.1002/mds.26073
Subject(s) - parkinson's disease , disease , gene , methylation , genetics , degenerative disease , medicine , biology , neuroscience , central nervous system disease
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. © 2014 International Parkinson and Movement Disorder Society