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The CRTAC1 protein in plasma associates with osteoarthritis and predicts progression to joint replacements : A Large-Scale Proteomics Scan in Iceland

The CRTAC1 protein in plasma associates with osteoarthritis and predicts progression to joint replacements : A Large-Scale Proteomics Scan in Iceland


Title: The CRTAC1 protein in plasma associates with osteoarthritis and predicts progression to joint replacements : A Large-Scale Proteomics Scan in Iceland
Author: Styrkarsdottir, Unnur   orcid.org/0000-0001-8146-8278
Lund, Sigrun H.
Sævarsdóttir, Sædís
Magnusson, Magnus I.
Gunnarsdottir, Kristbjorg
Norddahl, Gudmundur L.
Frigge, Michael L.
Ivarsdottir, Erna V.
Bjornsdottir, Gyda   orcid.org/0000-0002-8100-0306
Holm, Hilma   orcid.org/0000-0002-9517-6636
... 9 more authors Show all authors
Date: 2021-11
Language: English
Scope: 10
University/Institute: Landspitali - The National University Hospital of Iceland
School: School of Health Sciences
Department: Faculty of Medicine
Clinical Laboratory Services, Diagnostics and Blood Bank
Internal Medicine and Emergency Services
Series: Arthritis and Rheumatology; 73(11)
ISSN: 2326-5191
DOI: https://doi.org/10.1002/art.41793
Subject: 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
URI: https://hdl.handle.net/20.500.11815/3223

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Citation:

Styrkarsdottir , U , Lund , S H , Sævarsdóttir , S , Magnusson , M I , Gunnarsdottir , K , Norddahl , G L , Frigge , M L , Ivarsdottir , E V , Bjornsdottir , G , Holm , H , Thorgeirsson , G , Rafnar , T , Jónsdóttir , I , Ingvarsson , Þ , Jónsson , H , Sulem , P , Thorsteinsdottir , U , Gudbjartsson , D & Stefansson , K 2021 , ' The CRTAC1 protein in plasma associates with osteoarthritis and predicts progression to joint replacements : A Large-Scale Proteomics Scan in Iceland ' , Arthritis and Rheumatology , vol. 73 , no. 11 , pp. 2025-2034 . https://doi.org/10.1002/art.41793

Abstract:

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 occurrence of OA and predictive of progression to joint replacement. This biomarker might also be useful in the selection of suitable patients for clinical trial enrollment.

Description:

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.

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