Genetic variability in the SNCA gene influences α-synuclein levels in the blood and brain
Genetic variability in the SNCA gene influences α-synuclein levels in the blood and brain
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DOI：
10.1096/fj.07-9348com
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发表时间：
2008-05-01
期刊：
影响因子：
4.8
通讯作者：
Gasser, Thomas
中科院分区：
文献类型：
--
作者：
Fuchs, Julia;Tichopad, Ales;Gasser, Thomas
编码α-突触核蛋白的SNCA基因的启动子和3'区的遗传变异性调节发生散发性帕金森病（PD）的风险。这是否是通过调节α-突触核蛋白表达水平介导的仍然未知。因此，我们分析了α-突触核蛋白在血液和人类死后的脑组织，包括黑质，使用定量实时逆转录酶-聚合酶链反应和酶联免疫吸附试验在体内的水平。单核苷酸多态性（SNP）rs356219是SNCA基因3'区域中疾病相关单倍型的标记SNP，其对黑质和小脑中的SNCA mRNA水平具有显著影响。此外，PD相关启动子重复序列NACP-Rep 1的“保护性”基因型259/259与血液中比基因型261/261、259/261和259/263更低的蛋白水平相关。总之，我们提供的证据表明，α-突触核水平的SNCA基因的启动子和3'区在体内的遗传变异性的影响。
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.