University Clinic, Department of Neurology, University of Bonn, Bonn, Germany.
Neurogenetics. 2012 Feb;13(1):87-91. doi: 10.1007/s10048-011-0308-3. Epub 2012 Jan 12.
Multiple lines of evidence suggest a link between environmental toxins and Parkinson's disease (PD). Although numerous studies reported associations of genetic variants in de-toxifying enzymes, i.e. cytochrome genes, with PD. Epigenetic modifications of genes and subsequent altered expression may confer a yet unappreciated level of susceptibility. We present a genome-wide methylation analysis of PD with quantitative DNA methylation levels of 27.500 CpG sites representing 14.495 genes. We found decreased methylation of the cytochrome P450 2E1 gene and increased expression of CYP2E1 messenger RNA in PD patients' brains, suggesting that epigenetic variants of this cytochrome contribute to PD susceptibility.
有多项证据表明环境毒素与帕金森病(PD)之间存在关联。虽然许多研究报告了解毒酶(如细胞色素基因)中的遗传变异与 PD 之间的关联,但基因的表观遗传修饰及其随后的表达改变可能赋予了尚未被认识到的易感性水平。我们对 PD 进行了全基因组甲基化分析,定量分析了代表 14495 个基因的 27500 个 CpG 位点的 DNA 甲基化水平。我们发现 PD 患者大脑中的细胞色素 P450 2E1 基因甲基化水平降低,CYP2E1 信使 RNA 表达增加,这表明该细胞色素的表观遗传变异可能导致 PD 易感性。