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Clinical Chemistry and Laboratory Medicine (CCLM)

Published in Association with the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM)

Editor-in-Chief: Plebani, Mario

Ed. by Gillery, Philippe / Greaves, Ronda / Lackner, Karl J. / Lippi, Giuseppe / Melichar, Bohuslav / Payne, Deborah A. / Schlattmann, Peter


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Independent association of plasma xanthine oxidoreductase activity with serum uric acid level based on stable isotope-labeled xanthine and liquid chromatography/triple quadrupole mass spectrometry: MedCity21 health examination registry

Masafumi KurajohORCID iD: https://orcid.org/0000-0002-2571-9375 / Shinya Fukumoto
  • Department of Premier Preventive Medicine, Osaka City University Graduate School of Medicine, Osaka, Japan
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/ Masanori Emoto
  • Department of Metabolism, Endocrinology, and Molecular Medicine, Osaka City University Graduate School of Medicine, Osaka, Japan
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/ Takayo Murase / Takashi Nakamura / Takuma Ishihara / Hirofumi Go
  • Department of Medical Statistics, Osaka City University Graduate School of Medicine, Osaka, Japan
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/ Kouji Yamamoto / Shinya Nakatani
  • Department of Metabolism, Endocrinology, and Molecular Medicine, Osaka City University Graduate School of Medicine, Osaka, Japan
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/ Akihiro Tsuda
  • Department of Metabolism, Endocrinology, and Molecular Medicine, Osaka City University Graduate School of Medicine, Osaka, Japan
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/ Shinsuke Yamada
  • Department of Metabolism, Endocrinology, and Molecular Medicine, Osaka City University Graduate School of Medicine, Osaka, Japan
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/ Tomoaki Morioka
  • Department of Metabolism, Endocrinology, and Molecular Medicine, Osaka City University Graduate School of Medicine, Osaka, Japan
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/ Katsuhito Mori / Yasuo Imanishi
  • Department of Metabolism, Endocrinology, and Molecular Medicine, Osaka City University Graduate School of Medicine, Osaka, Japan
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/ Masaaki Inaba
  • Department of Metabolism, Endocrinology, and Molecular Medicine, Osaka City University Graduate School of Medicine, Osaka, Japan
  • Department of Nephrology, Osaka City University Graduate School of Medicine, Osaka, Japan
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Published Online: 2019-05-14 | DOI: https://doi.org/10.1515/cclm-2019-0199

Abstract

Background

We developed a novel high-sensitive assay for plasma xanthine oxidoreductase (XOR) activity that is not affected by the original serum uric acid level. However, the association of plasma XOR activity with that level has not been fully examined.

Methods

This cross-sectional study included 191 subjects (91 males, 100 females) registered in the MedCity21 health examination registry. Plasma XOR activity was determined using our assay for plasma XOR activity with [13C2,15N2] xanthine and liquid chromatography/triple quadrupole mass spectrometry. Serum levels of uric acid and adiponectin, and visceral fat area (VFA) obtained by computed tomography were measured, and insulin resistance was determined based on the homeostasis model assessment (HOMA-IR) index.

Results

The median values for uric acid and plasma XOR activity were 333 μmol/L and 26.1 pmol/h/mL, respectively. Multivariable linear regression analysis showed a significant and positive association of serum uric acid level (coefficient: 26.503; 95% confidence interval: 2.06, 50.945; p = 0.035) with plasma XOR activity independent of VFA and HOMA-IR, and also age, gender, alcohol drinking habit, systolic blood pressure, estimated glomerular filtration rate (eGFR), glycated hemoglobin A1c, triglyceride, and adiponectin levels. The “gender*XOR activity” interaction was not significant (p = 0.91), providing no evidence that gender modifies the relationship between plasma XOR activity and serum uric acid level.

Conclusions

Plasma XOR activity was found to be positively associated with serum uric acid level independent of other known confounding factors affecting that level, including gender difference, eGFR, adiponectin level, VFA, and HOMA-IR.

Keywords: insulin resistance; plasma XOR activity; uric acid; visceral obesity

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About the article

Corresponding author: Masafumi Kurajoh, MD, PhD, Department of Metabolism, Endocrinology, and Molecular Medicine, Osaka City University Graduate School of Medicine, 1-4-3, Asahi-machi, Abeno-ku, Osaka 545-8585, Japan, Phone: +81-6-6645-3806, Fax: +81-6-6645-3808


Received: 2019-02-21

Accepted: 2019-04-04

Published Online: 2019-05-14


Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.

Research funding: This study was supported in part by research grants from Sanwa Kagaku Kenkyusho (to M.K.), Taisho Toyama Pharmaceutical Co. (to S.F.), Takeda Pharmaceuticals (to S.F.), Mitsubishi Tanabe Pharma Corporation (to S.F.), Chugai Pharmaceutical Co. (to S.F.), and Astellas Pharma (to S.F.) (funder Id: http://dx.doi.org/10.13039/501100004948), as well the Osaka City University (OCU) Strategic Research Grant 2014, 2015, 2016 for top priority research (to S.F.), a grant-in-aid for scientific research from the Gout Research Foundation (to M.K.), and a JSPS KAKENHI grant (number 18K11132) (to S.F.).

Employment or leadership: None declared.

Honorarium: None declared.

Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.


Citation Information: Clinical Chemistry and Laboratory Medicine (CCLM), 20190199, ISSN (Online) 1437-4331, ISSN (Print) 1434-6621, DOI: https://doi.org/10.1515/cclm-2019-0199.

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