Sun Jiahong, Zhao Min, Yang Liu, Liu Xue, Pacifico Lucia, Chiesa Claudio, Xi Bo
Department of Epidemiology, School of Public Health, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China.
Department of Nutrition and Food Hygiene, School of Public Health, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China.
Int J Hypertens. 2021 Aug 24;2021:6691734. doi: 10.1155/2021/6691734. eCollection 2021.
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.
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.
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 < 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 < 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.
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.
针对成年人的研究表明，多种代谢途径中的几种代谢物与高血压密切相关。然而，据我们所知，尚无研究在儿童中调查此类关联。因此，我们比较了血压正常和血压升高儿童的血清代谢物谱，以确定可能有助于评估儿童高血压的潜在代谢标志物和途径。
该研究纳入了26名高血压儿童（年龄范围6至11岁）和26名年龄及性别匹配的血压正常儿童，这些儿童来自桓台儿童心血管健康队列研究的基线调查。采用超高效液相色谱-四极杆飞行时间质谱法评估血清代谢物谱。在对体重指数、腰围和血脂谱进行调整后，使用逻辑回归分析选择与高血压相关的显著代谢物。利用京都基因与基因组百科全书（KEGG）和MetaboAnalyst搜索代谢物的潜在途径。
分别在正离子和负离子模式下初步筛选出45种和34种代谢物（投影变量重要性（VIP）>1.0且P<0.05）。在对错误发现率进行调整后，正离子和负离子模式下分别有7种和1种差异代谢物仍具有显著性（VIP>1.0且P<0.05）。这些代谢物主要参与氨基酸代谢和甘油磷脂代谢。其中，包括乙醇胺和2-甲基-3-羟基-5-甲酰基吡啶-4-羧酸在内的两种显著代谢物的曲线下面积值为0.820（95%置信区间，0.688-0.951），灵敏度为0.846，特异性为0.769。
非靶向代谢组学方法有效地识别了高血压儿童和非高血压儿童的差异血清代谢物谱。值得注意的是，包括乙醇胺和2-甲基-3-羟基-5-甲酰基吡啶-4-羧酸在内的两种代谢物在识别高血压儿童方面表现出良好的判别能力，为儿童高血压的潜在机制提供了新的见解。
