帕金森病患者外周血单核细胞常染色体上印迹位点和IGF2的DNA甲基化不受影响

O. Kaut, Amit Sharma, U. Wüllner
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引用次数: 7

摘要

基因组印记是一种表观遗传现象,导致等位基因的差异表达取决于他们的亲本来源。DNA甲基化在基因组印迹中的功能意义已被广泛研究,迄今为止,在人类中已鉴定出大约100个印迹基因。为了研究这些“已知”印迹基因的甲基化状态是否与帕金森病(PD)相关,我们使用Illumina的450K甲基化芯片分析了所有这些“已知”印迹基因的甲基化谱。引人注目的是,这些常染色体注释基因中没有一个显示PD和健康个体之间DNA甲基化的变化。通过亚硫酸氢盐测序PCR (BSP)和考虑不同剂量的左旋多巴,我们进一步完善了我们的分析,评估了母体印迹人类基因编码胰岛素样生长因子2 (IGF2)的DNA甲基化。我们的研究结果表明,PD患者IGF2基因外显子8-9基因组区域的甲基化谱既不受左旋多巴治疗剂量的影响,也不受疾病本身的影响。因此,常染色体印迹的丢失或破坏似乎在PD中并不明显,与疾病的发病机制无关。
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DNA Methylation of Imprinted Loci on Autosomal Chromosomes and IGF2 are not Affected in Parkinson's Disease Patients Peripheral Blood Monocytes
Genomic imprinting is an epigenetic phenomenon that results in differential expression of alleles depending on their parental origin. The functional significance of DNA methylation in genomic imprinting has been widely investigated and to date, around 100 imprinted genes have been identified in humans. To investigate, if methylation status of these “known” imprinting genes is associated with Parkinson's disease (PD), we analyzed methylation profile of all these “known” imprinting genes using an epigenome wide approach with Illumina's 450K methylation chip. Strikingly, none of these total autosomal annotated genes show changes of DNA methylation between PD and healthy individuals. We further refined our analysis by evaluating DNA methylation for maternally imprinted human gene encoding insulin-like growth factor 2 (IGF2) by using bisulfite sequencing PCR (BSP) and by considering different dosages of L-dopa. Our results demonstrate that methylation profiles specifically at exon 8-9 genomic region of IGF2 gene in PD are neither influenced by the dosage of L-dopa treatment nor by the disease itself. Thus loss or disruption of imprinting in autosomal chromosomes seems not to apparent in PD and is not relevant for the pathogenesis of the disease.
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