The CRTAC1 Protein in Plasma Is Associated With Osteoarthritis and Predicts Progression to Joint Replacement: A Large-Scale Proteomics Scan in Iceland : A Large-Scale Proteomics Scan in Iceland

• Published in: Arthritis & Rheumatology
• Main Authors: Styrkarsdottir, Unnur, Lund, S.H., Saevarsdottir, S., Magnusson, M.I., Gunnarsdottir, K., Norddahl, Gudmundur L., Frigge, Michael L., Ivarsdottir, E.V., Bjornsdottir, Gyda, Holm, Hilma, Thorgeirsson, Guðmundur, Rafnar, T., Jonsdottir, I., Ingvarsson, T., Jonsson, H., Sulem, P., Thorsteinsdottir, U., Gudbjartsson, Daniel Fannar, Stefansson, K., Thorgeirsson, Gudmundur, Ingvarsson, Þorvaldur
• Other Authors: Faculty of Physical Sciences, Faculty of Medicine, Internal Medicine and Emergency Services, Faculty of Earth Sciences, Clinical Laboratory Services, Diagnostics and Blood Bank, Health Sciences, School of Health Sciences, Landspitali - The National University Hospital of Iceland
• Format: Article in Journal/Newspaper
• Language: English
• Published: 2021
• Subjects: Liðskiptaaðgerðir; Prótín; Slitgigt; Adult; Aged; Arthroplasty; Replacement; Biomarkers/blood; Calcium-Binding Proteins/blood; Case-Control Studies; Disease Progression; Female; Humans; Iceland; Male; Middle Aged; Osteoarthritis/blood; Prospective Studies; Proteomics
• Online Access: https://hdl.handle.net/20.500.11815/4321; https://doi.org/10.1002/art.41793

Funding Information: The study is sponsored by deCODE genetics, Inc./Amgen Inc. The authors independently collected the data, interpreted the results, and had the final decision to submit the manuscript for publication. Publication of this article was not contingent upon approval by Amgen. Publisher Copyright: © 2021 The Authors. Arthritis & Rheumatology published by Wiley Periodicals LLC on behalf of American College of Rheumatology. Objective: Biomarkers for diagnosis and progression of osteoarthritis (OA) are lacking. This study was undertaken to identify circulating biomarkers for OA that could predict disease occurrence and/or progression to joint replacement. Methods: Using the SomaScan platform, we measured 4,792 proteins in plasma from 37,278 individuals, of whom 12,178 individuals had OA and 2,524 had undergone joint replacement. We performed a case–control study for identification of potential protein biomarkers for hip, knee, and/or hand OA, and a prospective study for identification of biomarkers for joint replacement. Results: Among the large panel of plasma proteins assessed, cartilage acidic protein 1 (CRTAC1) was the most strongly associated with both OA diagnosis (odds ratio 1.46 [95% confidence interval 1.41–1.52] for knee OA, odds ratio 1.36 [95% confidence interval 1.29–1.43] for hip OA, and odds ratio 1.33 [95% confidence interval 1.26–1.40] for hand OA) and progression to joint replacement (hazard ratio 1.40 [95% confidence interval 1.30–1.51] for knee replacement and hazard ratio 1.31 [95% confidence interval 1.19–1.45] for hip replacement). Patients with OA who were in the highest quintile of risk of joint replacement, based on known risk factors (i.e., age, sex, and body mass index) and plasma CRTAC1 level, were 16 times more likely to undergo knee replacement within 5 years of plasma sample collection than those in the lowest quintile, and 6.5 times more likely to undergo hip replacement. CRTAC1 was not associated with other types of inflammatory arthritis. A specific protein ...