title: Parkinson's disease correlates with promoter methylation in the α-synuclein gene.
abstract: 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.
authors.affiliation: Department of Neurology, Oslo University Hospital, Oslo, Norway.
authors.forename: Lasse
authors.initials: L
authors.lastname: Pihlstrøm
authors.forename: Victoria
authors.initials: V
authors.lastname: Berge
authors.forename: Aina
authors.initials: A
authors.lastname: Rengmark
authors.forename: Mathias
authors.initials: M
authors.lastname: Toft
mesh_terms: D000328:Adult; D000368:Aged; D019175:DNA Methylation; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics*; D012333:RNA, Messenger; D051844:alpha-Synuclein / Q000235:genetics*
chemical_list: D012333:RNA, Messenger; D051844:alpha-Synuclein
keywords: Parkinson's disease; SNCA; epigenetics; methylation; quantitative-trait locus