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鉴定与儿童青春期提前相关的尿液生物标志物:一项非靶向代谢组学分析。

Identification of urine biomarkers associated with early puberty in children: An untargeted metabolomics analysis.

机构信息

Department of Maternal, Child and Adolescent Health, Anhui Medical University School of Public Health, Hefei, Anhui, China; Key Laboratory of Population Health Across Life Cycle, Anhui Medical University, Ministry of Education of the People's Republic of China, Hefei, Anhui, China.

Department of Maternal, Child and Adolescent Health, Anhui Medical University School of Public Health, Hefei, Anhui, China; Key Laboratory of Population Health Across Life Cycle, Anhui Medical University, Ministry of Education of the People's Republic of China, Hefei, Anhui, China; Anhui Provincial Key Laboratory of Population Health and Aristogenics, Anhui Medical University, Hefei, Anhui, China.

出版信息

Physiol Behav. 2023 Oct 15;270:114305. doi: 10.1016/j.physbeh.2023.114305. Epub 2023 Jul 27.

DOI:10.1016/j.physbeh.2023.114305
PMID:37507079
Abstract

A trend toward earlier pubertal maturation in both sexes has been shown in many countries. Early puberty affects an increasing proportion of children for reasons that remain obscure. Novel candidate biomarkers are strongly needed. We sought to apply untargeted metabolomic profiling to identify triggering mechanisms and candidate biomarkers in children with early puberty. Participants aged 7 - 12 years old were recruited directly from two elementary schools of Bengbu, Anhui Province, China, from Feb 2021 to May 2021. Early puberty was determined by breast and testicular development at baseline (May 2021) and 6-month later. Ultra-high-performance liquid chromatography-based untargeted metabolomic profiling was performed on urine samples of children with early puberty and control subjects. Metabolomic profiling for early puberty in a sex dependent manner. For boys, we identified several perturbed pathways, including histidine metabolism, glycine, serine and threonine metabolism, and selenoamino acid metabolism, associated with early puberty. In contrast, there were differences in pyruvate metabolism, one carbon pool by folate, and D-glutamine and D-glutamate metabolism pathways in girls with early puberty compared with controls. In addition, 4-hydroxyhippuric acid and 5-methoxytryptophol were shown as potential independent diagnostic biomarker for early puberty in boys, 3-hydroxybenzoic acid and glutaminylproline were shown as early biomarker for early puberty in girls, achieving area under the ROC curve of 0.71 and 0.72 in discriminating early puberty boys, and 0.70 and 0.74 in discriminating early puberty girls from controls. Through metabolomic analysis, we have identified metabolic perturbations and potential biomarkers of early puberty.

摘要

在许多国家,男女的青春期成熟都呈现出提前的趋势。青春期提前影响了越来越多的儿童,其原因尚不清楚。因此,强烈需要新的候选生物标志物。我们试图应用非靶向代谢组学分析来鉴定青春期提前儿童的触发机制和候选生物标志物。

参与者年龄为 7-12 岁,直接从中国安徽省蚌埠市的两所小学招募,招募时间为 2021 年 2 月至 2021 年 5 月。青春期提前是通过基线(2021 年 5 月)和 6 个月后乳房和睾丸发育来确定的。对青春期提前的儿童和对照儿童的尿液样本进行基于超高效液相色谱的非靶向代谢组学分析。

以性别依赖的方式对青春期提前进行代谢组学分析。对于男孩,我们确定了几个受到干扰的途径,包括组氨酸代谢、甘氨酸、丝氨酸和苏氨酸代谢以及硒氨基酸代谢,与青春期提前有关。相比之下,青春期提前的女孩与对照组相比,在丙酮酸代谢、一碳池叶酸、D-谷氨酰胺和 D-谷氨酸代谢途径方面存在差异。此外,4-羟基苯乙酸和 5-甲氧基色醇被证明是男孩青春期提前的潜在独立诊断生物标志物,3-羟基苯甲酸和谷氨酰脯氨酸被证明是女孩青春期提前的早期生物标志物,在区分青春期提前的男孩时,ROC 曲线下面积分别为 0.71 和 0.72,在区分青春期提前的女孩和对照组时,ROC 曲线下面积分别为 0.70 和 0.74。

通过代谢组学分析,我们已经确定了青春期提前的代谢扰动和潜在的生物标志物。

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