Metabolomic profiling to develop blood biomarkers for Parkinson's disease
Metabolomic profiling to develop blood biomarkers for Parkinson's disease
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DOI：
10.1093/brain/awm304
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发表时间：
2008-02-01
期刊：
影响因子：
14.5
通讯作者：
Beal, M. Flint
中科院分区：
文献类型：
--
作者：
Bogdanov, Mikhail;Matson, Wayne R.;Beal, M. Flint
由于基于临床参数的诊断有相当大的错误率，开发用于帕金森病(PD)诊断和监测疾病进展的生物标志物具有重要意义。在这项研究中，我们利用高效液相色谱与电化学库仑阵列检测(LCECA)相结合的代谢组谱分析来寻找血浆中对帕金森病诊断有用的生物标志物。我们检查了25名对照组和66名帕金森病患者。我们还测量了8-羟基-2-脱氧鸟苷(8-OHdG)水平，作为DNA氧化损伤的标志。我们最初检查了未用药的PD受试者与对照组的资料，以排除对症药物的混杂影响。我们发现这两组人完全分开了。然后，我们确定了在区分两组中起到最大作用的变量，并将它们应用于服用多巴胺能药物的帕金森病患者。使用这些参数，我们实现了帕金森病患者和对照组的完全分离。8-OHdG水平在PD患者显著升高，但与对照组重叠。在我们的LCECA图谱中还测量了另外两个氧化损伤的标记物。PD患者尿酸显著降低，谷胱甘肽显著升高。这些发现表明，使用LCECA库仑阵列进行代谢谱分析在开发用于诊断以及监测帕金森病疾病进展的生物标志物方面具有很大的前景。
The development of biomarkers for the diagnosis and monitoring disease progression in Parkinson's disease (PD) is of great importance since diagnosis based on clinical parameters has a considerable error rate. In this study, we utilized metabolomic profiling using high performance liquid chromatography coupled with electrochemical coulometric array detection (LCECA) to look for biomarkers in plasma useful for the diagnosis of PD. We examined 25 controls and 66 PD patients. We also measured 8-hydroxy-2-deoxyguanosine (8-OHdG) levels as a marker of oxidative damage to DNA. We initially examined the profiles of unmedicated PD subjects compared to controls to rule out confounding effects of symptomatic medications. We found a complete separation of the two groups. We then determined the variables, which played the greatest role in separating the two groups and applied them to PD subjects taking dopaminergic medications. Using these parameters, we achieved a complete separation of the PD patients from controls. 8-OHdG levels were significantly increased in PD patients, but overlapped controls. Two other markers of oxidative damage were measured in our LCECA profiles. Uric acid was significantly reduced while glutathione was significantly increased in PD patients. These findings show that metabolomic profiling with LCECA coulometric array has great promise for developing biomarkers for both the diagnosis, as well as monitoring disease progression in PD.