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Article Dans Une Revue Scientific Reports Année : 2020

Effect of congenital adrenal hyperplasia treated by glucocorticoids on plasma metabolome: a machine-learning-based analysis

Résumé

Background: Congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency leads to impaired cortisol biosynthesis. Treatment includes glucocorticoid supplementation. We studied the specific metabolomics signatures in CAH patients using two different algorithms. Methods: In a case-control study of CAH patients matched on sex and age with healthy control subjects, two metabolomic analyses were performed: one using MetaboDiff, a validated differential metabolomic analysis tool and the other, using Predomics, a novel machine-learning algorithm. Results: 168 participants were included (84 CAH patients). There was no correlation between plasma cortisol levels during glucocorticoid supplementation and metabolites in CAH patients. Indoleamine 2,3-dioxygenase enzyme activity was correlated with ACTH (rho coefficient = -0.25, p-value = 0.02), in CAH patients but not in controls subjects. Overall, 33 metabolites were significantly altered in CAH patients. Main changes came from: purine and pyrimidine metabolites, branched aminoacids, tricarboxylic acid cycle metabolites and associated pathways (urea, glucose, pentose phosphates). MetaboDiff identified 2 modules that were significantly different between both groups: aminosugar metabolism and purine metabolism. Predomics found several interpretable models which accurately discriminated the two groups (accuracy of 0.86 and AUROC of 0.9). Conclusion: CAH patients and healthy control subjects exhibit significant differences in plasma metabolomes, which may be explained by glucocorticoid supplementation.
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Dates et versions

inserm-02872323 , version 1 (17-06-2020)

Identifiants

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Lee S Nguyen, Edi Prifti, Farid Ichou, Monique Leban, Christian Funck-Brentano, et al.. Effect of congenital adrenal hyperplasia treated by glucocorticoids on plasma metabolome: a machine-learning-based analysis. Scientific Reports, 2020, 10 (1), pp.8859. ⟨10.1038/s41598-020-65897-y⟩. ⟨inserm-02872323⟩
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