Relationship between blood plasma and synovial fluid metabolite concentrations in patients with osteoarthritis.
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.


CONCLUSIONS
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.
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.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.
Weidong
W
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.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.
Sergei
S
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.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.
Erfan
E
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.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.
Yuhua
Y
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.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.
Patricia E
PE
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.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.
Edward
E
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.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.
Roger
R
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.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.
Glynn
G
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.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.
Andrew
A
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.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.
Guang
G
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.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.
Proton
P
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.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. guangju.zhai@med.mun.ca.
Guangju
G
Zhai
D000368:Aged; D019645:Arthroplasty, Replacement, Knee; D005260:Female; D006801:Humans; D007719:Knee Joint / Q000378:metabolism* / Q000601:surgery; D008297:Male; D008875:Middle Aged; D020370:Osteoarthritis, Knee / Q000097:blood / Q000378:metabolism* / Q000601:surgery; D013582:Synovial Fluid / Q000378:metabolism*; D053719:Tandem Mass Spectrometry
BLOOD; METABOLITE CONCENTRATIONS; OSTEOARTHRITIS; SYNOVIAL FLUID