Identification of Potential Metabolic Markers of Hypertension in Chinese Children
Jiahong Sun1, Min Zhao2, Liu Yang1
1Department of Epidemiology, School of Public Health, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China.
Insights
This study identified key serum metabolites in children with hypertension. Ethanolamine and 2-methyl-3-hydroxy-5-formylpyridine-4-carboxylate show promise for diagnosing pediatric hypertension.
Area of Science:
- Pediatric cardiovascular health
- Metabolomics
- Biomarker discovery
Background:
- Adult hypertension is linked to various metabolic pathways.
- Pediatric hypertension's metabolic associations remain understudied.
- This study investigates serum metabolite differences in hypertensive children.
Purpose of the Study:
- To identify differential serum metabolites in children with and without hypertension.
- To explore potential metabolic pathways associated with pediatric hypertension.
- To discover novel biomarkers for early detection of hypertension in children.
Main Methods:
- Untargeted metabolomics using ultrahigh-performance liquid chromatography-quadrupole time-of-flight-mass spectrometry.
- Analysis of serum samples from 26 hypertensive and 26 normotensive children (aged 6-11 years).
- Logistic regression and pathway analysis (KEGG, MetaboAnalyst) to identify significant metabolites and pathways.
Main Results:
- Identified differential metabolites primarily in amino acid and glycerophospholipid metabolism.
- Two metabolites, ethanolamine and 2-methyl-3-hydroxy-5-formylpyridine-4-carboxylate, were significantly associated with hypertension.
- These two metabolites demonstrated good discriminative ability (AUC 0.820) for identifying hypertensive children.
Conclusions:
- Untargeted metabolomics effectively revealed distinct serum metabolite profiles in pediatric hypertension.
- Ethanolamine and 2-methyl-3-hydroxy-5-formylpyridine-4-carboxylate show potential as diagnostic biomarkers for pediatric hypertension.
- Findings provide new insights into the metabolic underpinnings of hypertension in children.
Background:
Studies in adults have shown that several metabolites across multiple pathways are strongly associated with hypertension. However, as yet, to our knowledge, no study has investigated such association in childhood. We, therefore, compared the serum metabolite profile of children with normal and elevated blood pressure (BP) to identify potential metabolic markers and pathways that could be useful for the assessment of pediatric hypertension.
Methods:
The study included 26 hypertensive children (age range, 6-11 years) and 26 age- and sex-matched ones with normal BP, who were recruited from the baseline survey of the Huantai Childhood Cardiovascular Health Cohort Study. Ultrahigh-performance liquid chromatography-quadrupole time-of-flight-mass spectrometry was performed to assess the serum metabolite profile. Logistic regression analysis was used to select significant metabolites associated with hypertension after adjustment for body mass index, waist circumference, and lipid profile. Kyoto Encyclopedia of Genes and Genomes (KEGG) and MetaboAnalyst were utilized to search for the potential pathways of metabolites.
Results:
A total of 45 and 34 metabolites were preliminarily screened in positive and negative modes, respectively (variable importance in the projection (VIP) > 1.0 and P < 0.05). After adjustment for the false discovery rate, 7 and 1 differential metabolites in the positive and negative modes, respectively, remained significant (VIP > 1.0 and q < 0.05). These metabolites were mainly involved in amino acid metabolism and glycerophospholipid metabolism. Among these, two significant metabolites including ethanolamine and 2-methyl-3-hydroxy-5-formylpyridine-4-carboxylate displayed an area under the curve value of 0.820 (95% confidence interval, 0.688-0.951), with a sensitivity of 0.846 and a specificity of 0.769.
Conclusion:
The untargeted metabolomics approach effectively identified the differential serum metabolite profile in children with and without hypertension. Notably, two metabolites including ethanolamine and 2-methyl-3-hydroxy-5-formylpyridine-4-carboxylate exhibited a good discriminative ability to identify children with hypertension, providing new insights into potential mechanisms of pediatric hypertension.
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