The CRTAC1 Protein in Plasma Is Associated With Osteoarthritis and Predicts Progression to Joint Replacement: A Large-Scale Proteomics Scan in Iceland.
Journal
Arthritis & rheumatology (Hoboken, N.J.)
ISSN: 2326-5205
Titre abrégé: Arthritis Rheumatol
Pays: United States
ID NLM: 101623795
Informations de publication
Date de publication:
11 2021
11 2021
Historique:
received:
08
12
2020
accepted:
27
04
2021
pubmed:
14
5
2021
medline:
16
12
2021
entrez:
13
5
2021
Statut:
ppublish
Résumé
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. 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. 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. 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.
Identifiants
pubmed: 33982893
doi: 10.1002/art.41793
pmc: PMC8596997
doi:
Substances chimiques
Biomarkers
0
CRTAC1 protein, human
0
Calcium-Binding Proteins
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2025-2034Informations de copyright
© 2021 The Authors. Arthritis & Rheumatology published by Wiley Periodicals LLC on behalf of American College of Rheumatology.
Références
Biochem Biophys Res Commun. 2020 Oct 29;532(1):159-165
pubmed: 32838966
Semin Arthritis Rheum. 2013 Dec;43(3):303-13
pubmed: 23992801
Br Med Bull. 2013;105:185-99
pubmed: 23337796
Proc Natl Acad Sci U S A. 2017 Jan 31;114(5):E727-E732
pubmed: 28096410
Osteoarthritis Cartilage. 2014 May;22(5):683-9
pubmed: 24576742
Nat Genet. 2018 Dec;50(12):1681-1687
pubmed: 30374069
Nucleic Acids Res. 2011 Aug;39(15):e102
pubmed: 21646338
Osteoarthritis Cartilage. 2011 Dec;19(12):1396-404
pubmed: 22001901
BMC Musculoskelet Disord. 2017 Dec 2;18(1):508
pubmed: 29197369
Biochem J. 2001 Jan 15;353(Pt 2):169-74
pubmed: 11139377
Arthritis Rheum. 2013 Apr;65(4):981-92
pubmed: 23400684
Rheumatol Int. 2018 May;38(5):725-735
pubmed: 29098370
BMC Musculoskelet Disord. 2012 Feb 16;13:20
pubmed: 22340303
PLoS One. 2016 Jul 14;11(7):e0159157
pubmed: 27415616
Nat Commun. 2019 Mar 20;10(1):1284
pubmed: 30894546
Cell Physiol Biochem. 2016;39(6):2275-2286
pubmed: 27855397
Nat Rev Rheumatol. 2014 Jul;10(7):437-41
pubmed: 24662640
Osteoarthritis Cartilage. 2010 May;18(5):605-12
pubmed: 20175979
Nat Genet. 2019 Feb;51(2):230-236
pubmed: 30664745
Lancet. 2018 Nov 10;392(10159):1789-1858
pubmed: 30496104
Proteins. 2017 Feb;85(2):242-255
pubmed: 27862299
Int J Mol Sci. 2017 Mar 12;18(3):
pubmed: 28287489
Ann Intern Med. 2000 Oct 17;133(8):635-46
pubmed: 11033593
J Orthop Translat. 2017 Aug 15;13:50-57
pubmed: 29662791
Curr Opin Rheumatol. 2018 Jan;30(1):121-128
pubmed: 29040157
J Orthop Surg Res. 2018 Oct 19;13(1):262
pubmed: 30340615