Gout and hyperuricemia are highly prevalent metabolic diseases caused by high level of uric acid. Amino acids (AAs) involve in various biochemical processes including the biosynthesis of uric acid. However, the role of AAs in discriminating gout from hyperuricemia remains unknown. Here, we report that the plasma AAs profile can distinguish acute gout (AG) from asymptomatic hyperuricemia (AHU). We established an LC–MS/MS-based method to measure the plasma AAs without derivatization for the AG and AHU patients, and healthy controls. We found that the plasma profiling of AAs separated the AG patients from AHU patients and controls visually in both principal component analysis and orthogonal partial least-squares discriminant analysis (OPLS-DA) models. In addition, l-isoleucine, l-lysine, and l-alanine were suggested as the key mediators to distinguish the AG patients from AHU and control groups based on the S-plot analysis and variable importance in the projection values in the OPLS-DA models, volcano plot, and the receiver operating characteristic curves. In addition, the saturation of monosodium urate in the AA solutions at physiologically mimic status supported the changes in plasma AAs facilitating the precipitation of monosodium urate. This study suggests that l-isoleucine, l-lysine, and l-alanine could be the potential markers to distinguish the AG from AHU when the patients have similar blood levels of uric acid, providing new strategies for the prevention, treatment, and management of acute gout.
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This study was supported NSFC Grant 81470588 (J.-Y. L.). The authors would like to thank all the patients and healthy volunteers for the participation in this study.
Compliance with ethical standards
Conflict of interest
The authors declare no conflict of interest.
Research involving human participants and/or animals
The authors complied with the World Medical Association Declaration of Helsinki regarding the ethical conduct of research involving in human subjects. This study and the associated protocols for sample collection were approved by the Ethics Committee of Shanghai Tenth People’s Hospital (SHSY-IEC-KY-4.0/17–60/01).
Informed consent was obtained from all individual participants included in this study.
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