Plasma and urinary metabolomic profiles of Down syndrome correlate with alteration of mitochondrial metabolism

被引：59

作者：

Caracausi, Maria ^{[1
]}

Ghini, Veronica ^{[2
,3
]}

Locatelli, Chiara ^{[4
]}

Mericio, Martina ^{[5
]}

Piovesan, Allison ^{[1
]}

Antonaros, Francesca ^{[1
]}

Pelleri, Maria Chiara ^{[1
]}

Vitale, Lorenza ^{[1
]}

Vacca, Rosa Anna ^{[6
]}

Bedetti, Federica ^{[5
]}

Mimmi, Maria Chiara ^{[7
]}

Luchinat, Claudio ^{[2
,8
]}

Turano, Paola ^{[2
,8
]}

Strippoli, Pierluigi ^{[1
]}

Cocchi, Guido ^{[5
]}

机构：

[1] Univ Bologna, Unit Histol Embryol & Appl Biol, Dept Expt Diagnost & Specialty Med DIMES, Via Belmeloro 8, I-40126 Bologna, BO, Italy

[2] Univ Florence, Ctr Magnet Resonance, CERM, Via Luigi Sacconi 6, I-50019 Florence, Italy

[3] CIRMMP, Via Luigi Sacconi 6, I-50019 Florence, Italy

[4] St Orsola Malpighi Polyclin, Neonatol Unit, Via Massarenti 9, I-40138 Bologna, BO, Italy

[5] Univ Bologna, Dept Med & Surg Sci DIMEC, St Orsola Malpighi Polyclin, Neonatol Unit, Via Massarenti 9, I-40138 Bologna, BO, Italy

[6] CNR, Inst Biomembranes Bioenerget & Mol Biotechnol, Via Amendola 165-A, I-70126 Bari, Italy

[7] Univ Udine, Dept Med & Biol Sci, Ple Massimiliano Kolbe 4, I-33100 Udine, Italy

[8] Univ Florence, Dept Chem, Via Lastruccia 3, I-50019 Florence, Italy

来源：

SCIENTIFIC REPORTS | 2018年 / 8卷

关键词：

TRIMETHYLAMINE N-OXIDE; GUT MICROBIOTA; AMINO-ACIDS; NMR-SPECTROSCOPY; AMNIOTIC-FLUID; CHILDREN; DYSFUNCTION; TMAO; IMPAIRMENT; EXPRESSION;

D O I：

10.1038/s41598-018-20834-y

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页数：16

共 82 条

[1]

ABASHEVA GK, 1981, ZH NEVROPATOL PSIKH, V81, P1068

[2] Metabolic profile of amniotic fluid as a biochemical tool to screen for inborn errors of metabolism and fetal anomalies [J].