Genetic variability in the SNCA gene influences alpha-synuclein levels in the blood and brain.
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.
Fuchs
Julia
J
University of Tübingen, Hertie-Institute for Clinical Brain Research, Department of Neurodegenerative Diseases, Hoppe-Seyler Str. 3, 72076 Tübingen, Germany.
Tichopad
Ales
A
Golub
Yulia
Y
Munz
Marita
M
Schweitzer
Katherine J
KJ
Wolf
Björn
B
Berg
Daniela
D
Mueller
Jakob C
JC
Gasser
Thomas
T
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*
D012333:RNA, Messenger; C497604:SNCA protein, human; D051844:alpha-Synuclein