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核糖体DNA甲基化模式能否用作阿尔茨海默病的标志物?

Can the rDNA methylation pattern be used as a marker for Alzheimer's disease?

作者信息

Sperança Márcia Aparecida, Batista Lisandra Mesquita, Lourenço Ricardo da Silva, Tavares Wagner Malagó, Bertolucci Paulo Henrique Ferreira, Rigolin Valdeci de Oliveira Santos, Payão Spencer Luiz Marques, Smith Marília de Arruda Cardoso

机构信息

Disciplina de Biologia Molecular, Marília Medical School, Marília, SP, Brazil.

出版信息

Alzheimers Dement. 2008 Nov;4(6):438-42. doi: 10.1016/j.jalz.2008.03.010.

Abstract

BACKGROUND

Differential methylation activity of the human rDNA in Alzheimer's disease (AD) patients has been demonstrated by classic cytogenetic tools, indicating a decrease in rRNA gene expression. Methylation of CpGs is an important epigenetic mechanism involved in gene expression repression of tandem repeating genes during ageing. Thus, rDNA specific methylation pattern could be involved in AD and be used as a marker of the disease or of its progression.

METHODS

The methylation pattern of three rDNA regions, including the promoter, 18S, and 28S, was investigated with the use of restriction endonucleases sensitive to methylation and Southern blotting from DNA extracted from total peripheral blood cells of 28 AD patients and 28 elderly and young controls.

RESULTS

We did not find a significant divergence in the methylation pattern of the studied regions and in the relative amount of rDNA methylated copies among the individuals' groups.

CONCLUSIONS

No differential methylation pattern of rDNA genes was observed in total peripheral blood cells in aged and AD subjects by the methodology used.

摘要

背景

经典细胞遗传学工具已证明阿尔茨海默病(AD)患者中人类核糖体DNA(rDNA)存在差异甲基化活性,这表明rRNA基因表达降低。CpG甲基化是一种重要的表观遗传机制,参与衰老过程中串联重复基因的基因表达抑制。因此,rDNA特异性甲基化模式可能与AD有关,并可作为该疾病或其进展的标志物。

方法

使用对甲基化敏感的限制性内切酶和Southern印迹法,对28例AD患者以及28例老年和年轻对照者外周血全血细胞提取的DNA中三个rDNA区域(包括启动子、18S和28S)的甲基化模式进行了研究。

结果

我们未发现所研究区域的甲基化模式以及个体组中rDNA甲基化拷贝的相对数量存在显著差异。

结论

采用该方法未在老年和AD受试者的外周血全血细胞中观察到rDNA基因的差异甲基化模式。

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