Preliminary study of patients with chronic mountain sickness by GC-TOF-MS based serum metabolomics analysis

AIM: To evaluate specific metabolomics profiles in the serum of patients with chronic mountain sickness (CMS) and to explore the potential metabolic biomarkers in the native Tibetans living on the Qinghai-Tibet Pla-teau.METHODS: A gas chromatography time-of-flight mass spectrometry (GC-TOF-MS) approach as a metabolomics technique was used to evaluate metabolic differences. The native Tibetan CMS patients (n=10) and healthy Tibetan controls (n=10) were enrolled from YuShu in Qinghai province in this study. The serum samples were collected and analyzed by GC-TOF-MS coupled with a series of multivariate statistical analyses such as principal component analysis (PCA), partial least squares discriminant analysis (PLS-DA) and orthogonal partial least squares discriminant analysis (OPLS-DA).RESULTS: The intergroup differences between CMS patients and control subjects have been observed. A list of differential metabolites and several top altered metabolic pathways have been identified. The levels of fumaric acid, an intermediate in the tricarboxylic acid (TCA) cycle, and inosine were highly upregulated in the CMS patients, suggesting a greater effort to hypoxic adaptation in high elevation area. Other differential metabolites, such as methyl phosphate, 2-ketoadipate, lyxose and phytanic acid were also identified. Importantly, the differential metabolites possessed higher area under the ROC curve (AUC) values, indicating an excellent clinical ability for the prediction of CMS. Increased levels of amino acids (isoleucine, glycine, serine, L-cysteine, citrulline and trimethyllysine) were detected in CMS group, yet significantly decreased levels of sulfuric acid, oxamic acid, lyxose and glutamine were also detected in CMS group than those in control group. At the same time, the levels of ribose and glucose-1-phosphate were markedly elevated in CMS group (P<0.05).CONCLUSION: The metabolic activities are significantly altered in the serum of CMS patients. High altitude hypoxia may act on the disturbed glucose metabolism and amino acid metabolism in part of the Tibetan triggered by CMS.