Abstract

Objectives Gout is a common type of inflammatory arthritis. The aim of this study was to detect urinary metabolic changes in gout patients which may contribute to understanding the pathological mechanism of gout and discovering potential metabolite markers. Methods Urine samples from 35 gout patients and 29 healthy volunteers were analyzed by gas chromatography–mass spectrometry (GC–MS). Orthogonal partial least-squares discriminant analysis (OPLS-DA) was performed to screen differential metabolites between two groups, and the variable importance for projection (VIP) values and Student's t-test results were combined to define the significant metabolic changes caused by gout. Further, binary logistic regression analysis was performed to establish a model to distinguish gout patients from healthy people, and receiver operating characteristic (ROC) curve was made to evaluate the potential for diagnosis of gout. Result A total of 30 characteristic metabolites were significantly different between gout patients and controls, mainly including amino acids, carbohydrates, organic acids, and their derivatives, associated with perturbations in purine nucleotide synthesis, amino acid metabolism, purine metabolism, lipid metabolism, carbohydrate metabolism, and tricarboxylic acid cycle. Binary logistic regression and ROC curve analysis showed the combination of urate and isoxanthopterin can effectively discriminate the gout patients from controls with the area under the curve (AUC) of 0.879. Conclusion Thus, the urinary metabolomics study is an efficient tool for a better understanding of the metabolic changes of gout, which may support the clinical diagnosis and pathological mechanism study of gout.

Highlights

  • Gout, a common type of arthritis that features by deposits of monosodium urate crystals in the articular cavity or synovial fluid, is always accompanied by sudden joint inflammatory reaction [1,2,3]

  • We were able to discriminate gout patients from healthy controls in an Orthogonal partial least-squares discriminant analysis (OPLS-DA) model based on urinary metabolites, and 30 significantly different metabolites were identified which were mainly involved in purine nucleotide synthesis, amino acid metabolism, purine metabolism, lipid metabolism, carbohydrate metabolism, and tricarboxylic acid (TCA) cycle (Figure 5)

  • Our study suggested that reduced amino acid levels and increased isoxanthopterin level in gout patients may indicate a disorder of the metabolism of one-carbon units and nucleic acid synthesis and appears to be associated with the acceleration of purine nucleotide synthesis in patients

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Summary

Introduction

A common type of arthritis that features by deposits of monosodium urate crystals in the articular cavity or synovial fluid, is always accompanied by sudden joint inflammatory reaction [1,2,3]. The incidence of gout has reportedly experienced continuous growth over the last few decades around the world. Great advance has been made in investigating the pathogenesis of gout. There remains some uncertainty about the pathogeny of gout which raises the difficulties in its prevention, diagnosis, and treatment. The gold standard of gout diagnosis involves an invasive test of synovial fluid for the presence of monosodium urate crystals [6], but does not always work in clinical practice. It is desirable to develop a more accurate, rapid, and reliable diagnostic method on the diagnosis of gout

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