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中国 12-17 岁青少年高血压患者的血清代谢物。

Serum metabolites of hypertension among Chinese adolescents aged 12-17 years.

机构信息

Department of Epidemiology, School of Public Health, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China.

Department of Children and Adolescents Health Care, School of Public Health, Ningxia Medical University, Ningxia, China.

出版信息

J Hum Hypertens. 2022 Oct;36(10):925-932. doi: 10.1038/s41371-021-00602-8. Epub 2021 Sep 3.

Abstract

The regulatory mechanisms of hypertension in youth are incompletely understood. We aimed to identify potential serum metabolic alterations associated with hypertension in adolescents. A 1:1 age- and sex-matched case-control study including 30 hypertensive adolescents aged 12-17 years and 30 normotensive adolescents for the training set and 14 hypertensive adolescents and 14 normotensive adolescents for the test set was performed, which came from one cross-sectional study in Ningxia, China. Hypertension was defined based on blood pressure (BP) values measured on three different occasions according to the BP reference of Chinese children and adolescents. Untargeted ultra-high-performance liquid tandem chromatography quadrupole time of flight mass spectrometry was used to identify differential metabolites between hypertensive and normotensive adolescents. A total of 77 metabolites in positive mode and 101 in negative mode were identified (VIP > 1.0 and P < 0.05). After adjustment for the false discovery rate, 4 differential metabolites in positive mode and 10 in negative mode were found (Q value < 0.05). The logistic regression model adjusted for body mass index and lipid profile selected four significant metabolites (4-hydroxybutanoic acid, L-serine, acetone, and pterostilbene). The main metabolic pathways of amino acid metabolism, pantothenate and CoA biosynthesis, glyoxylate and dicarboxylate metabolism, fructose and mannose metabolism, and linoleic acid metabolism may contribute to the development of hypertension in Chinese adolescents. Based on the receiver operating characteristic plot, 4-hydroxybutanoic acid, L-serine, acetone, and pterostilbene may preliminarily help distinguish hypertension from normal BP in adolescents, with AUC values of 0.857 in the training set and 0.934 in the test set. The identified metabolites and pathways may foster a better understanding of hypertension pathogenesis in Chinese adolescents.

摘要

青少年高血压的调控机制尚不完全清楚。我们旨在鉴定与青少年高血压相关的潜在血清代谢改变。这是一项在中国宁夏进行的横断面研究,包括 30 名年龄在 12-17 岁的高血压青少年和 30 名血压正常的青少年作为训练集,以及 14 名高血压青少年和 14 名血压正常的青少年作为测试集,进行了 1:1 的年龄和性别匹配的病例对照研究。高血压的定义基于三次不同场合测量的血压(BP)值,根据中国儿童和青少年的 BP 参考值进行。采用靶向超高效液相串联色谱-四极杆飞行时间质谱法鉴定高血压和血压正常青少年之间的差异代谢物。在正模式下鉴定到 77 种代谢物,在负模式下鉴定到 101 种代谢物(VIP>1.0 和 P<0.05)。经过错误发现率校正后,在正模式下发现 4 种差异代谢物,在负模式下发现 10 种差异代谢物(Q 值<0.05)。经过体重指数和脂质谱调整的逻辑回归模型选择了 4 种显著代谢物(4-羟基丁酸、L-丝氨酸、丙酮和紫檀芪)。氨基酸代谢、泛酸和辅酶 A 生物合成、乙醛酸和二羧酸代谢、果糖和甘露糖代谢以及亚油酸代谢的主要代谢途径可能有助于中国青少年高血压的发展。基于受试者工作特征曲线,4-羟基丁酸、L-丝氨酸、丙酮和紫檀芪可能初步有助于区分青少年的高血压与正常血压,在训练集中的 AUC 值为 0.857,在测试集中的 AUC 值为 0.934。鉴定出的代谢物和途径可能有助于更好地理解中国青少年高血压的发病机制。

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