Genetic variability in the SNCA gene influences α-synuclein levels in the blood and brain

被引：206

作者：

Fuchs, Julia ^{[1
]}

Tichopad, Ales ^{[2
]}

Golub, Yulia ^{[1
]}

Munz, Marita ^{[1
]}

Schweitzer, Katherine J. ^{[1
]}

Wolf, Bjoern ^{[1
]}

Berg, Daniela ^{[1
]}

Mueller, Jakob C. ^{[1
,3
]}

Gasser, Thomas ^{[1
]}

机构：

[1] Univ Tubingen, Hertie Inst Clin Brain Res, Dept Neurodegenerat Dis, D-72076 Tubingen, Germany

[2] Tech Univ Munich, Freising Weihenstephan, Germany

[3] Max Planck Inst Ornithol, Dept Behav Ecol & Evolut Genet, Seewiesen, Germany

来源：

FASEB JOURNAL | 2008年 / 22卷 / 05期

关键词：

Parkinson's disease; SNP; NACP-Rep1; substantia nigra; gene expression; real-time RT-PCR; ELISA;

D O I：

10.1096/fj.07-9348com

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 [生物化学与分子生物学]; 081704 [应用化学];

摘要：

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-synuclei levels are influenced by genetic variability in the promoter and 3' region of the SNCA gene in vivo.

引用

页码：1327 / 1334

页数：8

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