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

• Published in: Arthritis & Rheumatology
• Main Authors: Styrkarsdottir, Unnur, Lund, Sigrun H, Saevarsdottir, Saedis, Magnusson, Magnus I, Gunnarsdottir, Kristbjorg, Norddahl, Gudmundur L, Frigge, Michael L, Ivarsdottir, Erna V, Bjornsdottir, Gyda, Holm, Hilma, Thorgeirsson, Gudmundur, Rafnar, Thorunn, Jonsdottir, Ingileif, Ingvarsson, Thorvaldur, Jonsson, Helgi, Sulem, Patrick, Thorsteinsdottir, Unnur, Gudbjartsson, Daniel, Stefansson, Kari
• Other Authors: 1deCODE genetics, Inc., Reykjavik, Iceland. 2deCODE genetics, Inc., University of Iceland, and Landspitali, Reykjavik, Iceland, and Karolinska Institutet, Stockholm, Sweden. 3deCODE genetics, Inc., University of Iceland, and Landspitali, Reykjavik, Iceland. 4University of Akureyri and Akureyri Hospital, Akureyri, Iceland, and University of Iceland, Reykjavik, Iceland. 5University of Iceland and Landspitali, Reykjavik, Iceland. 6deCODE Genetics, Inc., and University of Iceland, Reykjavik, Iceland.
• Format: Article in Journal/Newspaper
• Language: English
• Published: Wiley 2022
• Subjects: Slitgigt; Liðskiptaaðgerðir; Sjúkdómsgreining; Osteoarthritis; Biomarkers; Disease Progression; Arthroplasty; Replacement; Iceland
• Online Access: http://hdl.handle.net/2336/622013; https://doi.org/10.1002/art.41793

To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked Download 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 profile was identified in those patients who had undergone joint replacement prior to plasma sample collection. Conclusion: Through a hypothesis-free approach, we identified CRTAC1 in plasma as a novel promising candidate biomarker for OA that is both associated with ...