Guangju Zhai1, Xianbang Sun2, Edward W Randell3, Ming Liu4, Na Wang5, Irina Tolstykh6, Proton Rahman7, James Torner8, Cora E Lewis9, Michael C Nevitt6, Ali Guermazi10, Frank Roemer10, David T Felson11. 1. G. Zhai, PhD, M. Liu, MSc, Discipline of Genetics, Faculty of Medicine, Memorial University of Newfoundland, St. John's, Newfoundland, Canada; guangju.zhai@med.mun.ca. 2. X. Sun, MS, Department of Rheumatology, Boston University School of Medicine, Boston, USA. 3. E. Randell, PhD, Division of Laboratory Medicine, Faculty of Medicine, Memorial University of Newfoundland, St. John's, Newfoundland, Canada. 4. G. Zhai, PhD, M. Liu, MSc, Discipline of Genetics, Faculty of Medicine, Memorial University of Newfoundland, St. John's, Newfoundland, Canada. 5. N. Wang, PhD, Biostatistics and Epidemiology Data Analytics Center, Boston University School of Public Health, Boston, USA. 6. I. Tolstykh, MS, M.C. Nevitt, PhD, MPH, Epidemiology and Biostatistics, University of California, San Francisco, USA. 7. P. Rahman, MD, Discipline of Medicine, Faculty of Medicine, Memorial University of Newfoundland, St. John's, Newfoundland, Canada. 8. J. Torner, PhD, Department of Epidemiology, University of Iowa, Iowa City, Iowa, USA. 9. C.E. Lewis, MD, Department of Epidemiology, University of Alabama, Birmingham, USA. 10. A. Guermazi, MD, PhD, F. Roemer, MD, Department of Radiology, Boston University School of Medicine, Boston, USA. 11. D.T. Felson, MD, MPH, Department of Rheumatology, Boston University School of Medicine, Boston, USA, and NIHR Manchester Biomedical Research Centre, Manchester Academic Health Science Centre, Manchester University NHS Foundation Trust, Manchester, UK.
Abstract
OBJECTIVE: To identify plasma markers associated with an increased risk of radiographic knee osteoarthritis(OA) progression using a metabolomics approach. METHODS: Study participants were from the Multicenter Osteoarthritis Study (MOST) and were categorized into 2 groups based on the presence of baseline radiographic OA. Subjects in group 1 had unilateral knee OA and subjects in group 2 had bilateral knee OA. Progression was defined as a half-grade or greater worsening in joint space width at 30-month follow-up. For group 1, a participant progressed when their OA knee showed radiographic progression and the contralateral knee developed OA; for group 2, a participant progressed when both knees with OA showed radiographic progression. Metabolomic profiling was performed on plasma samples collected at baseline and logistic regression was performed to test the association between each metabolite and knee OA progression after adjustment for age, sex, BMI, and clinic site. Significance was defined as P ≤ 0.0003 in the combined analysis. RESULTS: There were 234 progressors (57 in group 1 and 177 in group 2) and 322 nonprogressors (206 in group 1 and 116 in group 2) included in the analyses. Among 157 metabolites studied, we found that odds of progression were 1.46 times higher per SD increase of phenylalanine level (95% CI 1.20-1.77, P = 0.0001) in the combined analysis. Sex-specific analysis showed that an association was seen in women (P = 0.0002) but not in men. CONCLUSION: Our data suggest that phenylalanine might be a novel plasma marker for higher risk of bilateral radiographic knee OA progression in women.
OBJECTIVE: To identify plasma markers associated with an increased risk of radiographic knee osteoarthritis(OA) progression using a metabolomics approach. METHODS: Study participants were from the Multicenter Osteoarthritis Study (MOST) and were categorized into 2 groups based on the presence of baseline radiographic OA. Subjects in group 1 had unilateral knee OA and subjects in group 2 had bilateral knee OA. Progression was defined as a half-grade or greater worsening in joint space width at 30-month follow-up. For group 1, a participant progressed when their OA knee showed radiographic progression and the contralateral knee developed OA; for group 2, a participant progressed when both knees with OA showed radiographic progression. Metabolomic profiling was performed on plasma samples collected at baseline and logistic regression was performed to test the association between each metabolite and knee OA progression after adjustment for age, sex, BMI, and clinic site. Significance was defined as P ≤ 0.0003 in the combined analysis. RESULTS: There were 234 progressors (57 in group 1 and 177 in group 2) and 322 nonprogressors (206 in group 1 and 116 in group 2) included in the analyses. Among 157 metabolites studied, we found that odds of progression were 1.46 times higher per SD increase of phenylalanine level (95% CI 1.20-1.77, P = 0.0001) in the combined analysis. Sex-specific analysis showed that an association was seen in women (P = 0.0002) but not in men. CONCLUSION: Our data suggest that phenylalanine might be a novel plasma marker for higher risk of bilateral radiographic knee OA progression in women.
Authors: David T Felson; Michael C Nevitt; Mei Yang; Margaret Clancy; Jingbo Niu; James C Torner; C Elizabeth Lewis; Piran Aliabadi; Burton Sack; Charles McCulloch; Yuqing Zhang Journal: J Rheumatol Date: 2008-09-15 Impact factor: 4.666
Authors: Ian J Wallace; Steven Worthington; David T Felson; Robert D Jurmain; Kimberly T Wren; Heli Maijanen; Robert J Woods; Daniel E Lieberman Journal: Proc Natl Acad Sci U S A Date: 2017-08-14 Impact factor: 11.205
Authors: Guangju Zhai; Rui Wang-Sattler; Deborah J Hart; Nigel K Arden; Alan J Hakim; Thomas Illig; Tim D Spector Journal: Ann Rheum Dis Date: 2010-04-13 Impact factor: 19.103
Authors: R F Loeser; W Pathmasiri; S J Sumner; S McRitchie; D Beavers; P Saxena; B J Nicklas; J Jordan; A Guermazi; D J Hunter; S P Messier Journal: Osteoarthritis Cartilage Date: 2016-03-21 Impact factor: 6.576
Authors: Neil A Segal; Michael C Nevitt; K Douglas Gross; Keith D Gross; Jean Hietpas; Natalie A Glass; Cora E Lewis; James C Torner Journal: PM R Date: 2013-08 Impact factor: 2.298
Authors: James A Gallagher; Jane P Dillon; Nicolas Sireau; Oliver Timmis; Lakshminarayan R Ranganath Journal: Semin Cell Dev Biol Date: 2016-02-16 Impact factor: 7.727
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Authors: Ming Liu; Yiheng Huang; Hongwei Zhang; Dawn Aitken; Michael C Nevitt; Jason S Rockel; Jean-Pierre Pelletier; Cora E Lewis; James Torner; Yoga Raja Rampersaud; Anthony V Perruccio; Nizar N Mahomed; Andrew Furey; Edward W Randell; Proton Rahman; Guang Sun; Johanne Martel-Pelletier; Mohit Kapoor; Graeme Jones; David Felson; Dake Qi; Guangju Zhai Journal: Metabolites Date: 2022-04-07