deCODE genetics/Amgen Inc., Reykjavik, Iceland.
deCODE genetics/Amgen Inc., Faculty of Medicine, School of Health Sciences, University of Iceland, Department of Medicine, and Landspitali The National University Hospital of Iceland, Reykjavik, Iceland.
Arthritis Rheumatol. 2023 Apr;75(4):544-552. doi: 10.1002/art.42376. Epub 2022 Dec 28.
The level of cartilage acidic protein 1 (CRTAC1) in plasma was recently discovered to be associated with osteoarthritis (OA) risk and progression to joint replacement in Iceland. This study was undertaken to validate these findings in an independent population.
In this study, 1,462 plasma proteins were measured in 54,265 participants from the UK Biobank on the Olink Explore platform. We analyzed the association of plasma proteins with prevalent OA, incident OA, and progression to joint replacement. We assessed the specificity of OA association through comparison of associations with inflammatory joint diseases and with previous joint replacement.
The CRTAC1 protein showed the strongest association with prevalent knee OA (odds ratio [OR] 1.34 [95% confidence interval (95% CI) 1.27, 1.41]) and was associated with hip OA (OR 1.19 [95% CI 1.11, 1.28]). It predicted incident diagnosis of OA in the knee (hazard ratio [HR] 1.40 [95% CI 1.35, 1.46]) and hip (HR 1.25 [95% CI 1.19, 1.31]), as well as progression to joint replacement (HR 1.20 [95% CI 1.08, 1.33] for the knee and HR 1.22 [95% CI 1.08, 1.38] for the hip), while no association was found with inflammatory joint diseases. Individuals in the highest quintile of risk based on CRTAC1 level, age, sex, and body mass index had a 10-fold risk of knee or hip OA within 5 years compared to those in the lowest quintile. Adding aggrecan core protein (ACAN) and neurocan core protein (NCAN) to the model improved the prediction of OA but not joint replacement. Furthermore, we replicated the association of CUB domain-containing protein 1 with prior joint replacement.
Plasma CRTAC1 is a specific biomarker for OA and a predictor of OA risk and progression to joint replacement. Adding ACAN and NCAN protein levels to the CRTAC1 model improved the prediction of OA.
最近发现，血浆中软骨酸性蛋白 1（CRTAC1）的水平与骨关节炎（OA）的风险和关节置换有关。本研究旨在验证这些发现是否适用于独立人群。
本研究在英国生物库的 54265 名参与者中使用 Olink Explore 平台测量了 1462 种血浆蛋白。我们分析了血浆蛋白与现患 OA、新发 OA 和进展至关节置换的相关性。我们通过比较与炎症性关节疾病和既往关节置换的相关性来评估 OA 相关性的特异性。
CRTAC1 蛋白与现患膝关节 OA 相关性最强（比值比[OR] 1.34[95%置信区间（95%CI）1.27，1.41]），与髋关节 OA 相关（OR 1.19[95%CI 1.11，1.28]）。它预测膝关节（风险比[HR]1.40[95%CI 1.35，1.46]）和髋关节（HR 1.25[95%CI 1.19，1.31]）OA 的新发诊断，以及进展至关节置换（膝关节 HR 1.20[95%CI 1.08，1.33]和髋关节 HR 1.22[95%CI 1.08，1.38]），但与炎症性关节疾病无关。基于 CRTAC1 水平、年龄、性别和体重指数，风险最高五分位的个体在 5 年内膝关节或髋关节 OA 的风险是风险最低五分位的个体的 10 倍。在模型中加入聚集蛋白（ACAN）和神经蛋白聚糖核心蛋白（NCAN）可改善 OA 的预测，但不能改善关节置换的预测。此外，我们复制了 CUB 结构域蛋白 1 与既往关节置换的相关性。
血浆 CRTAC1 是 OA 的特异性生物标志物，可预测 OA 风险和进展至关节置换。将 ACAN 和 NCAN 蛋白水平加入 CRTAC1 模型可改善 OA 的预测。
