Molecular markers of early Parkinson's disease based on gene expression in blood
Molecular markers of early Parkinson's disease based on gene expression in blood
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DOI：
10.1073/pnas.0610204104
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发表时间：
2007-01-16
影响因子：
11.1
通讯作者：
Gullans, Steven R.
中科院分区：
文献类型：
--
作者：
Scherzer, Clemens R.;Eklund, Aron C.;Gullans, Steven R.
帕金森氏病（PD）的进展无情，影响全世界500万人。PD的实验室检查对于开发旨在减缓或预防疾病进展的治疗至关重要。我们对105名个体进行了全转录组扫描，以询问早期PD患者细胞血液中扰动的分子过程。在包括健康和疾病对照的训练集的66个样本中，此处鉴定的分子多基因标记物与PD风险相关[第三个三分位数交叉验证的比值比为5.7（趋势P为0.005）]。在39个独立测试样本中进一步验证[第三个三分位比值比为5.1（趋势P 0.04）]。PD患者与健康个体中差异表达的22个独特基因提供了对外周血中可检测到的疾病相关过程的见解。这些包括cochaperone ST 13，它稳定热休克蛋白70，一种α-突触核蛋白错误折叠和毒性的修饰剂。在两个独立人群中，PD患者的ST 13信使RNA拷贝数（平均值+/- SE 0.59 +/- 0.05）低于对照组（0.96 +/- 0.09）（P = 0.002）。因此，在血液中测量的基因表达信号可以促进PD生物标志物的开发。
Parkinson's disease (PD) progresses relentlessly and affects five million people worldwide. Laboratory tests for PD are critically needed for developing treatments designed to slow or prevent progression of the disease. We performed a transcriptome-wide scan in 105 individuals to interrogate the molecular processes perturbed in cellular blood of patients with early-stage PD. The molecular multigene marker here identified is associated with risk of PD in 66 samples of the training set comprising healthy and disease controls [third tertile cross-validated odds ratio of 5.7 (P for trend 0.005)]. It is further validated in 39 independent test samples [third tertile odds ratio of 5.1 (P for trend 0.04)]. Insights into disease-linked processes detectable in peripheral blood are offered by 22 unique genes differentially expressed in patients with PD versus healthy individuals. These include the cochaperone ST13, which stabilizes heat-shock protein 70, a modifier of alpha-synuclein misfolding and toxicity. ST13 messenger RNA copies are lower in patients with PD (mean +/- SE 0.59 +/- 0.05) than in controls (0.96 +/- 0.09) (P = 0.002) in two independent populations. Thus, gene expression signals measured in blood can facilitate the development of biomarkers for PD.