The Center for Neuropathology and Prion Research, Ludwig-Maximilians-University Munich, Feodor-Lynen-Str. 23, 81377, Munich, Germany.
Neuromolecular Med. 2011 Dec;13(4):310-20. doi: 10.1007/s12017-011-8163-9. Epub 2011 Nov 1.
The α-synuclein gene (SNCA) plays a major role in the aetiology of Lewy body disease (LBD) including Parkinson's disease (PD). Point mutations and genetic alterations causing elevated gene expression are causally linked to familial PD. To what extent epigenetic changes play a role in the regulation of α-synuclein expression and may contribute to the aetiology of sporadic LBD is a matter of debate. We analysed the methylation state of the promoter region and a CpG-rich region of intron 1 of α-synuclein in several brain regions in sporadic LBD and controls using 454 GS-FLX-based high-resolution bisulphite sequencing. Our results indicate that there are significant differences in the level of methylation between different brain areas. The overall methylation levels in the promoter and intron 1 of α-synuclein are rather low in controls and-in contrast to previously reported findings-are not significantly different from LBD. However, single CpG analysis revealed significant hyper- and hypomethylation at different positions in various brain regions and LBD stages. A slight overall increase in methylation related to LBD patients' age was detected.
α-突触核蛋白基因（SNCA）在包括帕金森病（PD）在内的路易体病（LBD）的发病机制中起主要作用。导致基因表达升高的点突变和遗传改变与家族性 PD 有因果关系。在 α-突触核蛋白表达的调控中，表观遗传变化起了多大作用，以及它们是否有助于散发性 LBD 的发病机制，这是一个有争议的问题。我们使用基于 454 GS-FLX 的高分辨率亚硫酸氢盐测序，在散发性 LBD 和对照的几个大脑区域分析了 α-突触核蛋白启动子区域和内含子 1 的 CpG 丰富区的甲基化状态。我们的结果表明，不同脑区之间的甲基化水平存在显著差异。在对照中，α-突触核蛋白启动子和内含子 1 的整体甲基化水平相当低，与之前的报道结果相反，与 LBD 也没有显著差异。然而，单个 CpG 分析显示，在不同的大脑区域和 LBD 阶段，不同位置存在显著的超甲基化和低甲基化。在 LBD 患者中还检测到与年龄相关的甲基化水平略有整体增加。
