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Research ArticleArticle

Relationship Between Blood Plasma and Synovial Fluid Metabolite Concentrations in Patients with Osteoarthritis

Weidong Zhang, Sergei Likhodii, Erfan Aref-Eshghi, Yuhua Zhang, Patricia E. Harper, Edward Randell, Roger Green, Glynn Martin, Andrew Furey, Guang Sun, Proton Rahman and Guangju Zhai
The Journal of Rheumatology March 2015, jrheum.141252; DOI: https://doi.org/10.3899/jrheum.141252
Weidong Zhang
From the Discipline of Genetics, Department of Laboratory Medicine, Department of Surgery, Discipline of Medicine, Faculty of Medicine, Memorial University of Newfoundland (MUN), St. John’s, Newfoundland, Canada; Department of Twin Research and Genetic Epidemiology, King’s College London, London, UK. Supported by the Canadian Institutes of Health Research (CIHR); Newfoundland and Labrador Research and Development Corporation; MUN. EAE is supported by the Dean’s PhD Fellowship, MUN; PEH is supported by the CIHR CGS-Master’s Award. W. Zhang, PhD, Postdoctoral Fellow, Discipline of Genetics; S. Likhodii, PhD, Assistant Professor, Department of Laboratory Medicine; E. Aref-Eshghi, MD, PhD student; Y. Zhang, MSc, Statistician; P.E. Harper, BSC, MSc student, Discipline of Genetics; E. Randell, PhD, Associate Professor, Department of Laboratory Medicine; R. Green, PhD, Professor, Discipline of Genetics; G. Martin, MD, Orthopedic Fellow; A. Furey, MD, Associate Professor, Department of Surgery; G. Sun, PhD, Professor; P. Rahman, MD, Professor, Discipline of Medicine, Faculty of Medicine, MUN; G. Zhai, PhD, Associate Professor, Discipline of Genetics, MUN, and Department of Twin Research and Genetic Epidemiology, King’s College London. Address correspondence to Dr. G. Zhai, Discipline of Genetics, Faculty of Medicine, Memorial University of Newfoundland, St. John’s, Newfoundland A1B 3V6, Canada. E-mail: guangju.zhai@med.mun.ca. Accepted for publication January 14, 2015.
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Sergei Likhodii
From the Discipline of Genetics, Department of Laboratory Medicine, Department of Surgery, Discipline of Medicine, Faculty of Medicine, Memorial University of Newfoundland (MUN), St. John’s, Newfoundland, Canada; Department of Twin Research and Genetic Epidemiology, King’s College London, London, UK. Supported by the Canadian Institutes of Health Research (CIHR); Newfoundland and Labrador Research and Development Corporation; MUN. EAE is supported by the Dean’s PhD Fellowship, MUN; PEH is supported by the CIHR CGS-Master’s Award. W. Zhang, PhD, Postdoctoral Fellow, Discipline of Genetics; S. Likhodii, PhD, Assistant Professor, Department of Laboratory Medicine; E. Aref-Eshghi, MD, PhD student; Y. Zhang, MSc, Statistician; P.E. Harper, BSC, MSc student, Discipline of Genetics; E. Randell, PhD, Associate Professor, Department of Laboratory Medicine; R. Green, PhD, Professor, Discipline of Genetics; G. Martin, MD, Orthopedic Fellow; A. Furey, MD, Associate Professor, Department of Surgery; G. Sun, PhD, Professor; P. Rahman, MD, Professor, Discipline of Medicine, Faculty of Medicine, MUN; G. Zhai, PhD, Associate Professor, Discipline of Genetics, MUN, and Department of Twin Research and Genetic Epidemiology, King’s College London. Address correspondence to Dr. G. Zhai, Discipline of Genetics, Faculty of Medicine, Memorial University of Newfoundland, St. John’s, Newfoundland A1B 3V6, Canada. E-mail: guangju.zhai@med.mun.ca. Accepted for publication January 14, 2015.
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Erfan Aref-Eshghi
From the Discipline of Genetics, Department of Laboratory Medicine, Department of Surgery, Discipline of Medicine, Faculty of Medicine, Memorial University of Newfoundland (MUN), St. John’s, Newfoundland, Canada; Department of Twin Research and Genetic Epidemiology, King’s College London, London, UK. Supported by the Canadian Institutes of Health Research (CIHR); Newfoundland and Labrador Research and Development Corporation; MUN. EAE is supported by the Dean’s PhD Fellowship, MUN; PEH is supported by the CIHR CGS-Master’s Award. W. Zhang, PhD, Postdoctoral Fellow, Discipline of Genetics; S. Likhodii, PhD, Assistant Professor, Department of Laboratory Medicine; E. Aref-Eshghi, MD, PhD student; Y. Zhang, MSc, Statistician; P.E. Harper, BSC, MSc student, Discipline of Genetics; E. Randell, PhD, Associate Professor, Department of Laboratory Medicine; R. Green, PhD, Professor, Discipline of Genetics; G. Martin, MD, Orthopedic Fellow; A. Furey, MD, Associate Professor, Department of Surgery; G. Sun, PhD, Professor; P. Rahman, MD, Professor, Discipline of Medicine, Faculty of Medicine, MUN; G. Zhai, PhD, Associate Professor, Discipline of Genetics, MUN, and Department of Twin Research and Genetic Epidemiology, King’s College London. Address correspondence to Dr. G. Zhai, Discipline of Genetics, Faculty of Medicine, Memorial University of Newfoundland, St. John’s, Newfoundland A1B 3V6, Canada. E-mail: guangju.zhai@med.mun.ca. Accepted for publication January 14, 2015.
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Yuhua Zhang
From the Discipline of Genetics, Department of Laboratory Medicine, Department of Surgery, Discipline of Medicine, Faculty of Medicine, Memorial University of Newfoundland (MUN), St. John’s, Newfoundland, Canada; Department of Twin Research and Genetic Epidemiology, King’s College London, London, UK. Supported by the Canadian Institutes of Health Research (CIHR); Newfoundland and Labrador Research and Development Corporation; MUN. EAE is supported by the Dean’s PhD Fellowship, MUN; PEH is supported by the CIHR CGS-Master’s Award. W. Zhang, PhD, Postdoctoral Fellow, Discipline of Genetics; S. Likhodii, PhD, Assistant Professor, Department of Laboratory Medicine; E. Aref-Eshghi, MD, PhD student; Y. Zhang, MSc, Statistician; P.E. Harper, BSC, MSc student, Discipline of Genetics; E. Randell, PhD, Associate Professor, Department of Laboratory Medicine; R. Green, PhD, Professor, Discipline of Genetics; G. Martin, MD, Orthopedic Fellow; A. Furey, MD, Associate Professor, Department of Surgery; G. Sun, PhD, Professor; P. Rahman, MD, Professor, Discipline of Medicine, Faculty of Medicine, MUN; G. Zhai, PhD, Associate Professor, Discipline of Genetics, MUN, and Department of Twin Research and Genetic Epidemiology, King’s College London. Address correspondence to Dr. G. Zhai, Discipline of Genetics, Faculty of Medicine, Memorial University of Newfoundland, St. John’s, Newfoundland A1B 3V6, Canada. E-mail: guangju.zhai@med.mun.ca. Accepted for publication January 14, 2015.
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Patricia E. Harper
From the Discipline of Genetics, Department of Laboratory Medicine, Department of Surgery, Discipline of Medicine, Faculty of Medicine, Memorial University of Newfoundland (MUN), St. John’s, Newfoundland, Canada; Department of Twin Research and Genetic Epidemiology, King’s College London, London, UK. Supported by the Canadian Institutes of Health Research (CIHR); Newfoundland and Labrador Research and Development Corporation; MUN. EAE is supported by the Dean’s PhD Fellowship, MUN; PEH is supported by the CIHR CGS-Master’s Award. W. Zhang, PhD, Postdoctoral Fellow, Discipline of Genetics; S. Likhodii, PhD, Assistant Professor, Department of Laboratory Medicine; E. Aref-Eshghi, MD, PhD student; Y. Zhang, MSc, Statistician; P.E. Harper, BSC, MSc student, Discipline of Genetics; E. Randell, PhD, Associate Professor, Department of Laboratory Medicine; R. Green, PhD, Professor, Discipline of Genetics; G. Martin, MD, Orthopedic Fellow; A. Furey, MD, Associate Professor, Department of Surgery; G. Sun, PhD, Professor; P. Rahman, MD, Professor, Discipline of Medicine, Faculty of Medicine, MUN; G. Zhai, PhD, Associate Professor, Discipline of Genetics, MUN, and Department of Twin Research and Genetic Epidemiology, King’s College London. Address correspondence to Dr. G. Zhai, Discipline of Genetics, Faculty of Medicine, Memorial University of Newfoundland, St. John’s, Newfoundland A1B 3V6, Canada. E-mail: guangju.zhai@med.mun.ca. Accepted for publication January 14, 2015.
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Edward Randell
From the Discipline of Genetics, Department of Laboratory Medicine, Department of Surgery, Discipline of Medicine, Faculty of Medicine, Memorial University of Newfoundland (MUN), St. John’s, Newfoundland, Canada; Department of Twin Research and Genetic Epidemiology, King’s College London, London, UK. Supported by the Canadian Institutes of Health Research (CIHR); Newfoundland and Labrador Research and Development Corporation; MUN. EAE is supported by the Dean’s PhD Fellowship, MUN; PEH is supported by the CIHR CGS-Master’s Award. W. Zhang, PhD, Postdoctoral Fellow, Discipline of Genetics; S. Likhodii, PhD, Assistant Professor, Department of Laboratory Medicine; E. Aref-Eshghi, MD, PhD student; Y. Zhang, MSc, Statistician; P.E. Harper, BSC, MSc student, Discipline of Genetics; E. Randell, PhD, Associate Professor, Department of Laboratory Medicine; R. Green, PhD, Professor, Discipline of Genetics; G. Martin, MD, Orthopedic Fellow; A. Furey, MD, Associate Professor, Department of Surgery; G. Sun, PhD, Professor; P. Rahman, MD, Professor, Discipline of Medicine, Faculty of Medicine, MUN; G. Zhai, PhD, Associate Professor, Discipline of Genetics, MUN, and Department of Twin Research and Genetic Epidemiology, King’s College London. Address correspondence to Dr. G. Zhai, Discipline of Genetics, Faculty of Medicine, Memorial University of Newfoundland, St. John’s, Newfoundland A1B 3V6, Canada. E-mail: guangju.zhai@med.mun.ca. Accepted for publication January 14, 2015.
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Roger Green
From the Discipline of Genetics, Department of Laboratory Medicine, Department of Surgery, Discipline of Medicine, Faculty of Medicine, Memorial University of Newfoundland (MUN), St. John’s, Newfoundland, Canada; Department of Twin Research and Genetic Epidemiology, King’s College London, London, UK. Supported by the Canadian Institutes of Health Research (CIHR); Newfoundland and Labrador Research and Development Corporation; MUN. EAE is supported by the Dean’s PhD Fellowship, MUN; PEH is supported by the CIHR CGS-Master’s Award. W. Zhang, PhD, Postdoctoral Fellow, Discipline of Genetics; S. Likhodii, PhD, Assistant Professor, Department of Laboratory Medicine; E. Aref-Eshghi, MD, PhD student; Y. Zhang, MSc, Statistician; P.E. Harper, BSC, MSc student, Discipline of Genetics; E. Randell, PhD, Associate Professor, Department of Laboratory Medicine; R. Green, PhD, Professor, Discipline of Genetics; G. Martin, MD, Orthopedic Fellow; A. Furey, MD, Associate Professor, Department of Surgery; G. Sun, PhD, Professor; P. Rahman, MD, Professor, Discipline of Medicine, Faculty of Medicine, MUN; G. Zhai, PhD, Associate Professor, Discipline of Genetics, MUN, and Department of Twin Research and Genetic Epidemiology, King’s College London. Address correspondence to Dr. G. Zhai, Discipline of Genetics, Faculty of Medicine, Memorial University of Newfoundland, St. John’s, Newfoundland A1B 3V6, Canada. E-mail: guangju.zhai@med.mun.ca. Accepted for publication January 14, 2015.
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Glynn Martin
From the Discipline of Genetics, Department of Laboratory Medicine, Department of Surgery, Discipline of Medicine, Faculty of Medicine, Memorial University of Newfoundland (MUN), St. John’s, Newfoundland, Canada; Department of Twin Research and Genetic Epidemiology, King’s College London, London, UK. Supported by the Canadian Institutes of Health Research (CIHR); Newfoundland and Labrador Research and Development Corporation; MUN. EAE is supported by the Dean’s PhD Fellowship, MUN; PEH is supported by the CIHR CGS-Master’s Award. W. Zhang, PhD, Postdoctoral Fellow, Discipline of Genetics; S. Likhodii, PhD, Assistant Professor, Department of Laboratory Medicine; E. Aref-Eshghi, MD, PhD student; Y. Zhang, MSc, Statistician; P.E. Harper, BSC, MSc student, Discipline of Genetics; E. Randell, PhD, Associate Professor, Department of Laboratory Medicine; R. Green, PhD, Professor, Discipline of Genetics; G. Martin, MD, Orthopedic Fellow; A. Furey, MD, Associate Professor, Department of Surgery; G. Sun, PhD, Professor; P. Rahman, MD, Professor, Discipline of Medicine, Faculty of Medicine, MUN; G. Zhai, PhD, Associate Professor, Discipline of Genetics, MUN, and Department of Twin Research and Genetic Epidemiology, King’s College London. Address correspondence to Dr. G. Zhai, Discipline of Genetics, Faculty of Medicine, Memorial University of Newfoundland, St. John’s, Newfoundland A1B 3V6, Canada. E-mail: guangju.zhai@med.mun.ca. Accepted for publication January 14, 2015.
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Andrew Furey
From the Discipline of Genetics, Department of Laboratory Medicine, Department of Surgery, Discipline of Medicine, Faculty of Medicine, Memorial University of Newfoundland (MUN), St. John’s, Newfoundland, Canada; Department of Twin Research and Genetic Epidemiology, King’s College London, London, UK. Supported by the Canadian Institutes of Health Research (CIHR); Newfoundland and Labrador Research and Development Corporation; MUN. EAE is supported by the Dean’s PhD Fellowship, MUN; PEH is supported by the CIHR CGS-Master’s Award. W. Zhang, PhD, Postdoctoral Fellow, Discipline of Genetics; S. Likhodii, PhD, Assistant Professor, Department of Laboratory Medicine; E. Aref-Eshghi, MD, PhD student; Y. Zhang, MSc, Statistician; P.E. Harper, BSC, MSc student, Discipline of Genetics; E. Randell, PhD, Associate Professor, Department of Laboratory Medicine; R. Green, PhD, Professor, Discipline of Genetics; G. Martin, MD, Orthopedic Fellow; A. Furey, MD, Associate Professor, Department of Surgery; G. Sun, PhD, Professor; P. Rahman, MD, Professor, Discipline of Medicine, Faculty of Medicine, MUN; G. Zhai, PhD, Associate Professor, Discipline of Genetics, MUN, and Department of Twin Research and Genetic Epidemiology, King’s College London. Address correspondence to Dr. G. Zhai, Discipline of Genetics, Faculty of Medicine, Memorial University of Newfoundland, St. John’s, Newfoundland A1B 3V6, Canada. E-mail: guangju.zhai@med.mun.ca. Accepted for publication January 14, 2015.
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Guang Sun
From the Discipline of Genetics, Department of Laboratory Medicine, Department of Surgery, Discipline of Medicine, Faculty of Medicine, Memorial University of Newfoundland (MUN), St. John’s, Newfoundland, Canada; Department of Twin Research and Genetic Epidemiology, King’s College London, London, UK. Supported by the Canadian Institutes of Health Research (CIHR); Newfoundland and Labrador Research and Development Corporation; MUN. EAE is supported by the Dean’s PhD Fellowship, MUN; PEH is supported by the CIHR CGS-Master’s Award. W. Zhang, PhD, Postdoctoral Fellow, Discipline of Genetics; S. Likhodii, PhD, Assistant Professor, Department of Laboratory Medicine; E. Aref-Eshghi, MD, PhD student; Y. Zhang, MSc, Statistician; P.E. Harper, BSC, MSc student, Discipline of Genetics; E. Randell, PhD, Associate Professor, Department of Laboratory Medicine; R. Green, PhD, Professor, Discipline of Genetics; G. Martin, MD, Orthopedic Fellow; A. Furey, MD, Associate Professor, Department of Surgery; G. Sun, PhD, Professor; P. Rahman, MD, Professor, Discipline of Medicine, Faculty of Medicine, MUN; G. Zhai, PhD, Associate Professor, Discipline of Genetics, MUN, and Department of Twin Research and Genetic Epidemiology, King’s College London. Address correspondence to Dr. G. Zhai, Discipline of Genetics, Faculty of Medicine, Memorial University of Newfoundland, St. John’s, Newfoundland A1B 3V6, Canada. E-mail: guangju.zhai@med.mun.ca. Accepted for publication January 14, 2015.
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Proton Rahman
From the Discipline of Genetics, Department of Laboratory Medicine, Department of Surgery, Discipline of Medicine, Faculty of Medicine, Memorial University of Newfoundland (MUN), St. John’s, Newfoundland, Canada; Department of Twin Research and Genetic Epidemiology, King’s College London, London, UK. Supported by the Canadian Institutes of Health Research (CIHR); Newfoundland and Labrador Research and Development Corporation; MUN. EAE is supported by the Dean’s PhD Fellowship, MUN; PEH is supported by the CIHR CGS-Master’s Award. W. Zhang, PhD, Postdoctoral Fellow, Discipline of Genetics; S. Likhodii, PhD, Assistant Professor, Department of Laboratory Medicine; E. Aref-Eshghi, MD, PhD student; Y. Zhang, MSc, Statistician; P.E. Harper, BSC, MSc student, Discipline of Genetics; E. Randell, PhD, Associate Professor, Department of Laboratory Medicine; R. Green, PhD, Professor, Discipline of Genetics; G. Martin, MD, Orthopedic Fellow; A. Furey, MD, Associate Professor, Department of Surgery; G. Sun, PhD, Professor; P. Rahman, MD, Professor, Discipline of Medicine, Faculty of Medicine, MUN; G. Zhai, PhD, Associate Professor, Discipline of Genetics, MUN, and Department of Twin Research and Genetic Epidemiology, King’s College London. Address correspondence to Dr. G. Zhai, Discipline of Genetics, Faculty of Medicine, Memorial University of Newfoundland, St. John’s, Newfoundland A1B 3V6, Canada. E-mail: guangju.zhai@med.mun.ca. Accepted for publication January 14, 2015.
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Guangju Zhai
From the Discipline of Genetics, Department of Laboratory Medicine, Department of Surgery, Discipline of Medicine, Faculty of Medicine, Memorial University of Newfoundland (MUN), St. John’s, Newfoundland, Canada; Department of Twin Research and Genetic Epidemiology, King’s College London, London, UK. Supported by the Canadian Institutes of Health Research (CIHR); Newfoundland and Labrador Research and Development Corporation; MUN. EAE is supported by the Dean’s PhD Fellowship, MUN; PEH is supported by the CIHR CGS-Master’s Award. W. Zhang, PhD, Postdoctoral Fellow, Discipline of Genetics; S. Likhodii, PhD, Assistant Professor, Department of Laboratory Medicine; E. Aref-Eshghi, MD, PhD student; Y. Zhang, MSc, Statistician; P.E. Harper, BSC, MSc student, Discipline of Genetics; E. Randell, PhD, Associate Professor, Department of Laboratory Medicine; R. Green, PhD, Professor, Discipline of Genetics; G. Martin, MD, Orthopedic Fellow; A. Furey, MD, Associate Professor, Department of Surgery; G. Sun, PhD, Professor; P. Rahman, MD, Professor, Discipline of Medicine, Faculty of Medicine, MUN; G. Zhai, PhD, Associate Professor, Discipline of Genetics, MUN, and Department of Twin Research and Genetic Epidemiology, King’s College London. Address correspondence to Dr. G. Zhai, Discipline of Genetics, Faculty of Medicine, Memorial University of Newfoundland, St. John’s, Newfoundland A1B 3V6, Canada. E-mail: guangju.zhai@med.mun.ca. Accepted for publication January 14, 2015.
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Abstract

Objective To investigate the relationship between plasma and synovial fluid (SF) metabolite concentrations in patients with osteoarthritis (OA).

Methods Blood plasma and SF samples were collected from patients with primary knee OA undergoing total knee arthroplasty. Metabolic profiling was performed by electrospray ionization tandem mass spectrometry using the AbsoluteIDQ kit. The profiling yielded 168 metabolite concentrations. Correlation analysis between SF and plasma metabolite concentrations was done on absolute concentrations as well as metabolite concentration ratios using Spearman’s rank correlation (ρ) method.

Results A total of 69 patients with knee OA were included, 30 men and 39 women, with an average age of 66 ± 8 years. For the absolute metabolite concentrations, the average ρ was 0.23 ± 0.13. Only 8 out of 168 metabolite concentrations had a ρ ≥ 0.45, with a p value ≤ 2.98 × 10-4, statistically significant after correcting multiple testing with the Bonferroni method. For the metabolite ratios (n = 28,056), the average ρ was 0.29 ± 0.20. There were 4018 metabolite ratios with a ρ ≥ 0.52 and a p value ≤ 1.78 × 10-6, significant after correcting multiple testing. Sex-separate analyses found no difference in ρ between men and women. Similarly, there was no difference in ρ between people younger and older than 65 years.

Conclusion Correlation between blood plasma and SF metabolite concentrations are modest. Metabolite ratios, which are considered proxies for enzymatic reaction rates and have higher correlations, should be considered when using blood plasma as a surrogate of SF in OA biomarker identification.

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Relationship Between Blood Plasma and Synovial Fluid Metabolite Concentrations in Patients with Osteoarthritis
Weidong Zhang, Sergei Likhodii, Erfan Aref-Eshghi, Yuhua Zhang, Patricia E. Harper, Edward Randell, Roger Green, Glynn Martin, Andrew Furey, Guang Sun, Proton Rahman, Guangju Zhai
The Journal of Rheumatology Mar 2015, jrheum.141252; DOI: 10.3899/jrheum.141252

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Relationship Between Blood Plasma and Synovial Fluid Metabolite Concentrations in Patients with Osteoarthritis
Weidong Zhang, Sergei Likhodii, Erfan Aref-Eshghi, Yuhua Zhang, Patricia E. Harper, Edward Randell, Roger Green, Glynn Martin, Andrew Furey, Guang Sun, Proton Rahman, Guangju Zhai
The Journal of Rheumatology Mar 2015, jrheum.141252; DOI: 10.3899/jrheum.141252
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