Plasma oxysterol profiling in children reveals 24-hydroxycholesterol as a potential marker for Autism Spectrum Disorders
Plasma oxysterol profiling in children reveals 24-hydroxycholesterol as a potential marker for Autism Spectrum Disorders
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DOI：
10.1016/j.biochi.2018.04.026
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发表时间：
2018-10-01
期刊：
影响因子：
3.9
通讯作者：
Iuliano, L.
中科院分区：
文献类型：
--
作者：
Grayaa, S.;Zerbinati, C.;Iuliano, L.
胆固醇及其含氧代谢产物，如氧化固醇，作为脑疾病病理生理学的潜在参与者被深入研究。已在患有多种神经精神障碍的患者中描述了改变的氧固醇水平，所述神经精神障碍包括阿尔茨海默病、肌萎缩性侧索硬化症、帕金森病、X连锁肾上腺脑白质营养不良和Smith-Lemli-Opitz综合征。最近的研究表明，自闭症谱系障碍与胆固醇代谢的破坏有关。本研究旨在调查自闭症谱系障碍患者血浆中氧化固醇的分布及其与临床参数的相关性。来自斯法克斯（突尼斯南部地区）的年龄和性别匹配的36名自闭症谱系障碍儿童和38名健康儿童被纳入研究。自闭症谱系障碍的严重程度使用儿童自闭症评定量表进行评估。使用标准技术测量标准脂质谱（总胆固醇、甘油三酯和高密度脂蛋白胆固醇）、血清葡萄糖、高敏C反应蛋白和类粘蛋白水平。通过同位素稀释气相色谱/质谱法测量氧固醇水平。两个研究人群的标准血脂、血糖、超敏C反应蛋白和类粘蛋白水平相似。与对照组相比，自闭症谱系障碍儿童的血浆24-羟基胆固醇水平显着较高，而7 α-羟基胆固醇和25-羟基胆固醇观察到临界显著性。在患者中，24-羟基胆固醇与年龄呈负相关。多变量分析表明，高血浆24-羟基胆固醇水平是自闭症谱系障碍的独立危险因素。另一方面，接收器的操作特性的分析证明，测量的参数记录令人满意的水平的特异性和sensitivity.The本研究提供的证据表明，自闭症谱系障碍与循环氧固醇水平的改变。这一发现表明，24-羟基胆固醇是一个独立的风险因素，这种疾病，并建议使用这种氧化固醇作为诊断工具，在自闭症谱系障碍。(C)2018 Elsevier B. V.和法国生物化学与生物分子学会（SFBBM）。All rights reserved.
Cholesterol and its oxygenated metabolites, such as oxysterols, are intensively investigated as potential players in the pathophysiology of brain disorder. Altered oxysterol levels have been described in patients with numerous neuropsychiatric disorders, including Alzheimer's disease, Amyotrophic Lateral Sclerosis, Parkinson's disease, X-linked adrenoleukodystrophy, and Smith-Lemli-Opitz Syndrome. Recent studies have shown that Autism Spectrum Disorders are associated with disruption of cholesterol metabolism. The present study aimed at investigating the profile of oxysterols in plasma and their association with clinical parameters in patients with Autism Spectrum Disorders. Thirty-six children with Autism Spectrum Disorders and thirty-eight healthy children, from Sfax (a southern area of Tunisia) matched for age and sex, were included in the study. The severity of Autism Spectrum Disorders was evaluated using the childhood autism rating scale. Standard lipid profile (total cholesterol, triglycerides, and high-density lipoprotein-cholesterol), serum glucose, high-sensitive C-reactive protein and orosomucoid levels were measured utilizing standard techniques. Oxysterol levels were measured by isotope-dilution gas chromatography/mass spectrometry. Standard lipid profile, serum glucose, high-sensitive C-reactive protein and orosomucoid levels were similar between the two studied populations. Compared to the control group, children with Autism Spectrum Disorders showed a significant higher plasma level of 24-hydroxycholesterol, while borderline significance was observed for 7 alpha-hydroxycholesterol, and 25-hydroxycholersterol. In patients, 24-hydroxycholesterol was inversely correlated with age. Multivariate analysis showed that high plasma levels of 24-hydroxycholesterol are independent risk factors for Autism Spectrum Disorders. On the other hand, an analysis of the receiver's operating characteristics proved that the measured parameters recorded satisfactory levels of specificity and sensitivity.The present study provides evidence that Autism Spectrum Disorders are associated with altered levels in circulating oxysterols. The finding that 24-hydroxycholesterol is an independent risk factor for the disease and suggests the use of this oxysterol as a diagnostic tool in Autism Spectrum Disorders. (C) 2018 Elsevier B.V. and Societe Francaise de Biochimie et Biologie Moleculaire (SFBBM). All rights reserved.