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Plasma profiling of amino acids distinguishes acute gout from asymptomatic hyperuricemia

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Abstract

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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Abbreviations

AA:

Amino acid

ACN:

Acetonitrile

AG:

Acute attack of gout, and acute gout

AHU:

Asymptomatic hyperuricemia

ESI:

Electrospray ionization

MeOH:

Methanol

PCA:

Principal component analysis

OPLS-DA:

Orthogonal partial least-squares discriminant analysis

MSU:

Monosodium urate

UA:

Uric acid

LOD:

Limit of detection

LOQ:

Limit of quantitation

DP:

Declustering potential

CE:

Collision energy

CXP:

Collision cell exit potential

SUS:

Shared and unique structures

VIP:

Variable importance in the projection

ROC:

Receiver operating characteristic

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Acknowledgements

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.

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Authors and Affiliations

  1. Center for Nephrology and Metabolomics and Division of Nephrology and Rheumatology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, 301 Mid Yanchang Rd, Shanghai, 200072, China

    Ying Luo, Ling Wang, Xin-Ying Liu, Ya-Xiang Song, Xin-Hua Li, Ai Peng & Jun-Yan Liu

  2. The School of Life Sciences and Technology, Shanghai Key Laboratory of Signaling and Disease Research, Tongji University, Shanghai, 200092, China

    Xiaolong Chen & Cizong Jiang

Authors
  1. Ying Luo
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  2. Ling Wang
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  3. Xin-Ying Liu
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  4. Xiaolong Chen
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  5. Ya-Xiang Song
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  6. Xin-Hua Li
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  8. Ai Peng
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  9. Jun-Yan Liu
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Correspondence to Ai Peng or Jun-Yan Liu.

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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).

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Informed consent was obtained from all individual participants included in this study.

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Handling Editor: D. Tsikas.

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Luo, Y., Wang, L., Liu, XY. et al. Plasma profiling of amino acids distinguishes acute gout from asymptomatic hyperuricemia. Amino Acids 50, 1539–1548 (2018). https://doi.org/10.1007/s00726-018-2627-2

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  • DOI: https://doi.org/10.1007/s00726-018-2627-2

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