title: Genetic variability in the SNCA gene influences alpha-synuclein levels in the blood and brain.
abstract: Genetic variability in the promoter and 3' region of the SNCA gene coding alpha-synuclein modulates the risk to develop sporadic Parkinson's disease (PD). Whether this is mediated by regulating alpha-synuclein expression levels remains unknown. Therefore, we analyzed levels of alpha-synuclein in blood and human post mortem brain tissue including the substantia nigra using quantitative real-time reverse transcriptase-polymerase chain reaction and enzyme linked immunosorbent assay in vivo. Single nucleotide polymorphism (SNP) rs356219, a tagging SNP for a disease-associated haplotype in the 3' region of the SNCA gene, has a significant effect on SNCA mRNA levels in the substantia nigra and the cerebellum. Further, the "protective" genotype 259/259 of the PD-associated promoter repeat NACP-Rep1 is associated with lower protein levels in blood than genotypes 261/261, 259/261, and 259/263. In conclusion, we provide evidence that alpha-synuclein levels are influenced by genetic variability in the promoter and 3' region of the SNCA gene in vivo.
authors.affiliation: University of Tübingen, Hertie-Institute for Clinical Brain Research, Department of Neurodegenerative Diseases, Hoppe-Seyler Str. 3, 72076 Tübingen, Germany.
authors.forename: Julia
authors.initials: J
authors.lastname: Fuchs
authors.forename: Ales
authors.initials: A
authors.lastname: Tichopad
authors.forename: Yulia
authors.initials: Y
authors.lastname: Golub
authors.forename: Marita
authors.initials: M
authors.lastname: Munz
authors.forename: Katherine J
authors.initials: KJ
authors.lastname: Schweitzer
authors.forename: Björn
authors.initials: B
authors.lastname: Wolf
authors.forename: Daniela
authors.initials: D
authors.lastname: Berg
authors.forename: Jakob C
authors.initials: JC
authors.lastname: Mueller
authors.forename: Thomas
authors.initials: T
authors.lastname: Gasser
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001923:Brain Chemistry / Q000235:genetics*; D002531:Cerebellum / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005838:Genotype; D006179:Gyrus Cinguli / Q000378:metabolism; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000737:chemistry; D008297:Male; D008526:Medulla Oblongata / Q000378:metabolism; D008875:Middle Aged; D010300:Parkinson Disease / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013378:Substantia Nigra / Q000378:metabolism; D013997:Time Factors; D051844:alpha-Synuclein / Q000032:analysis* / Q000097:blood / Q000235:genetics*
chemical_list: D012333:RNA, Messenger; C497604:SNCA protein, human; D051844:alpha-Synuclein