Identification of Potential Metabolic Markers of Hypertension in Chinese Children

Abstract

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.

Untargeted metabolomics analysis of differences in metabolite levels in congenital heart disease of varying severity

“…Mann-Whitney U tests, Student's t-tests, and Spearman correlation analyses were performed using SPSS 22.0. Metabolites shown by univariate analysis to have P < 0.05 and VIP > 1 on multivariate analysis were considered reliable differential metabolites [20]. For Spearman correlation analysis, P < 0.05 was considered signi cant [21].…”

Metabolome-Wide Association Study of Cord Blood Metabolites With Blood Pressure in Childhood and Adolescence

“…27 To our knowledge, only 2 small studies-both casecontrol in nature-have examined blood metabolite biomarkers with BP or hypertension in children. In 52 Chinese children (ages 6-11 years), Sun et al 28 identified 8 serum metabolites-mainly involved in amino acid and glycerophospholipid metabolism-associated with hypertension. In 456 Canadian children (age 5 years), Azab et al 29 found 13 metabolites associated with the risk of metabolic syndrome, of which BP is a component.…”

The association of dietary glutamine supplementation with the development of high salt-induced hypertension in rats

“…Conversely, another metabolomics study showed that systolic blood pressure (SBP) and pulse pressure are inversely correlated with glutamine in black adults (14). Similarly, our previous work identified that in children aged 6−11 years with elevated BP, the abundance of glutamine was lower than those with normal BP using a case-control design (15). L-citrulline, the metabolite of glutamine, can increase the synthesis of NO and inhibit arterial tension, which may be the way to regulate BP (16).…”