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帕金森病中的生物标志物:对携带和不携带PARK2和PARK8基因突变的患者外周血进行全基因表达分析。

Biomarkers in Parkinson Disease: global gene expression analysis in peripheral blood from patients with and without mutations in PARK2 and PARK8.

作者信息

Aguiar Patricia Maria de Carvalho, Severino Patricia

机构信息

Instituto Israelita de Ensino e Pesquisa Albert Einstein - IIEPAE, São Paulo, SP, BR.

出版信息

Einstein (Sao Paulo). 2010 Sep;8(3):291-7. doi: 10.1590/S1679-45082010AO1674.

Abstract

OBJECTIVE

To evaluate the performance of gene expression analysis in the peripheral blood of Parkinson disease patients with different genetic profiles using microarray as a tool to identify possible diseases related biomarkers which could contribute to the elucidation of the pathological process, as well as be useful in diagnosis.

METHODS

Global gene expression analysis by means of DNA microarrays was performed in peripheral blood of Parkinson disease patients with previously identified mutations in PARK2 or PARK8 genes, Parkinson disease patients without known mutations in these genes and normal controls. Each group consisted of five individuals.

RESULTS

Global gene expression profiles were heterogeneous among patients and controls, and it was not possible to detect a consistent pattern between groups. However, analyzing genes with differential expression of p < 0.005 and fold change ≥ 1.2, we were able to identify a small group of well-annotated genes.

CONCLUSIONS

Despite the small sample size, the identification of differentially expressed genes suggests that the microarray technique may be useful in identifying potential biomarkers in the peripheral blood of Parkinson disease patients or in people at risk of developing the disease. This will be important once neuroprotective therapies become available, and may contribute to the identification of new pathways involved in the disease physiopathology. Results presented here should be further validated in larger groups of patients.

摘要

目的

以基因芯片作为工具,评估不同基因谱帕金森病患者外周血中基因表达分析的性能,以识别可能有助于阐明病理过程且对诊断有用的疾病相关生物标志物。

方法

对先前已鉴定出PARK2或PARK8基因存在突变的帕金森病患者、这些基因无已知突变的帕金森病患者以及正常对照者的外周血进行DNA芯片全球基因表达分析。每组由五名个体组成。

结果

患者和对照者之间的全球基因表达谱存在异质性,且无法检测到组间一致的模式。然而,分析p<0.005且倍数变化≥1.2的差异表达基因时,我们能够鉴定出一小群注释良好的基因。

结论

尽管样本量较小,但差异表达基因的鉴定表明,基因芯片技术可能有助于在帕金森病患者或有患该病风险的人群外周血中识别潜在生物标志物。一旦有神经保护疗法可用,这将很重要,并且可能有助于识别疾病生理病理学中涉及的新途径。此处呈现的结果应在更大的患者群体中进一步验证。

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