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Serum metabolites of hypertension among Chinese adolescents aged 12–17 years

Journal of Human Hypertension volume 36, pages 925–932 (2022)Cite this article

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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.

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Fig. 1: OPLS-DA score plots for differentiating hypertensive and normotensive adolescents in the training set.
Fig. 2: Validation plots for the OPLS-DA model in the training set.
Fig. 3
Fig. 4: Analysis of ROC curves of three metabolites identified based on logistic regression analysis.

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Data availability

Data is available from the corresponding author BX (Email: xibo2007@126.com).

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Acknowledgements

We are thankful to the National Natural Science Foundation of China for the funding support.

Funding

This work was supported by the National Natural Science Foundation of China (81722039, 81673195).

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Author notes

  1. These authors contributed equally: Jiahong Sun, Wenqing Ding

Authors and Affiliations

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

    Jiahong Sun, Xue Liu & Bo Xi

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

    Wenqing Ding

  3. Department of Nutrition and Food Hygiene, School of Public Health, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China

    Min Zhao

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Contributions

Study design: BX. Data collection: WD, MZ. Analysis and interpretation of data: JS, XL. Drafting of the paper: JS, WD. Approval of the final version for publication: all the authors.

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Correspondence to Bo Xi.

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The study protocol was approved by the Institutional Ethics Review Board of the School of Public Health, Shandong University.

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Sun, J., Ding, W., Liu, X. et al. Serum metabolites of hypertension among Chinese adolescents aged 12–17 years. J Hum Hypertens 36, 925–932 (2022). https://doi.org/10.1038/s41371-021-00602-8

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