Metabolomic profiling in LRRK2-related Parkinson's disease.
Metabolomic profiling in LRRK2-related Parkinson's disease.
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DOI：
10.1371/journal.pone.0007551
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发表时间：
2009-10-22
期刊：
影响因子：
3.7
通讯作者：
Bogdanov M
中科院分区：
文献类型：
--
作者：
Johansen KK;Wang L;Aasly JO;White LR;Matson WR;Henchcliffe C;Beal MF;Bogdanov M
LRRK2基因突变是帕金森病（PD）最常见的遗传原因。我们使用代谢组学分析来鉴定与特发性和LRRK2 PD相关的生物标志物。我们比较了G2019S LRRK2突变导致的PD患者的血浆代谢组学特征，这些患者的无症状家族成员（有或无G2019S LRRK2突变），特发性PD患者以及非相关对照受试者。我们发现特发性PD和LRRK2 PD受试者的代谢组学特征与对照组明显分离。LRRK2 PD患者的代谢组学特征与特发性PD患者不同，这些特征可以预测PD是否继发于LRRK2突变或特发性。LRRK2 PD患者的代谢谱与其家族成员分离良好，但有和无LRRK2突变的家族成员之间存在轻微重叠。LRRK2和特发性PD患者均显示尿酸水平显著降低。我们还发现PD患者血浆中次黄嘌呤水平和嘌呤途径主要代谢产物的比例显著降低。这些发现表明，具有G2019S突变的LRRK2患者具有独特的代谢组学特征，将其与特发性PD患者区分开来。此外，无症状LRRK2携带者可以从基因阴性家族成员中分离出来，这提高了代谢组学谱可能有助于预测哪些LRRK2携带者最终会发展为PD的可能性。结果还表明，有畸变的嘌呤途径在PD可能发生上游尿酸。
Mutations in LRRK2 gene represent the most common known genetic cause of Parkinson's disease (PD). We used metabolomic profiling to identify biomarkers that are associated with idiopathic and LRRK2 PD. We compared plasma metabolomic profiles of patients with PD due to the G2019S LRRK2 mutation, to asymptomatic family members of these patients either with or without G2019S LRRK2 mutations, and to patients with idiopathic PD, as well as non-related control subjects. We found that metabolomic profiles of both idiopathic PD and LRRK2 PD subjects were clearly separated from controls. LRRK2 PD patients had metabolomic profiles distinguishable from those with idiopathic PD, and the profiles could predict whether the PD was secondary to LRRK2 mutations or idiopathic. Metabolomic profiles of LRRK2 PD patients were well separated from their family members, but there was a slight overlap between family members with and without LRRK2 mutations. Both LRRK2 and idiopathic PD patients showed significantly reduced uric acid levels. We also found a significant decrease in levels of hypoxanthine and in the ratios of major metabolites of the purine pathway in plasma of PD patients. These findings show that LRRK2 patients with the G2019S mutation have unique metabolomic profiles that distinguish them from patients with idiopathic PD. Furthermore, asymptomatic LRRK2 carriers can be separated from gene negative family members, which raises the possibility that metabolomic profiles could be useful in predicting which LRRK2 carriers will eventually develop PD. The results also suggest that there are aberrations in the purine pathway in PD which may occur upstream from uric acid.
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