Plasma and urinary metabolomic profiles of Down syndrome correlate with alteration of mitochondrial metabolism
Plasma and urinary metabolomic profiles of Down syndrome correlate with alteration of mitochondrial metabolism
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DOI：
10.1038/s41598-018-20834-y
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发表时间：
2018-02-14
影响因子：
4.6
通讯作者：
Cocchi, Guido
中科院分区：
文献类型：
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作者：
Caracausi, Maria;Ghini, Veronica;Cocchi, Guido
唐氏综合症 (DS) 是由人类 21 号染色体 (Hsa21) 的多余拷贝引起的，是智力障碍 (ID) 最常见的遗传原因。 DS 的主要特征是独特的面容和认知障碍。我们首次对血浆和尿液样本中代谢组的核磁共振 (NMR) 可检测部分进行了分析，研究了 67 名 DS 受试者和 29 名正常受试者作为 DS 兄弟姐妹中选择的对照。 NMR 代谢组图谱的多变量分析显示 DS 组和对照组之间存在明显区别（准确度高达 80%）。血浆和尿液的单变量分析揭示了一些有趣的代谢物的显着变化。值得注意的是，大多数改变的浓度与 3:2 基因剂量模型一致，表明血浆中 Hsa21 的三个拷贝而不是两个拷贝引起的影响：DS/正常比率为 1.23（丙酮酸盐）、1.47（琥珀酸盐）、1.39（富马酸盐）、1.33（乳酸盐）、1.4（甲酸盐）。在克雷布斯循环开始时或期间会产生几种显着改变的代谢物。考虑性别、年龄和禁食状态并没有显着影响多变量和单变量分析的主要结果。
Down syndrome (DS) is caused by the presence of a supernumerary copy of the human chromosome 21 (Hsa21) and is the most frequent genetic cause of intellectual disability (ID). Key traits of DS are the distinctive facies and cognitive impairment. We conducted for the first time an analysis of the Nuclear Magnetic Resonance (NMR)-detectable part of the metabolome in plasma and urine samples, studying 67 subjects with DS and 29 normal subjects as controls selected among DS siblings. Multivariate analysis of the NMR metabolomic profiles showed a clear discrimination (up to of 80% accuracy) between the DS and the control groups. The univariate analysis of plasma and urine revealed a significant alteration for some interesting metabolites. Remarkably, most of the altered concentrations were consistent with the 3: 2 gene dosage model, suggesting effects caused by the presence of three copies of Hsa21 rather than two: DS/normal ratio in plasma was 1.23 (pyruvate), 1.47 (succinate), 1.39 (fumarate), 1.33 (lactate), 1.4 (formate). Several significantly altered metabolites are produced at the beginning or during the Krebs cycle. Accounting for sex, age and fasting state did not significantly affect the main result of both multivariate and univariate analysis.