Fu Qingsong, Yuan Xinhua, Wang Weibin, Han Xinyou, Zhang Jiakai, Wu Junlong, Wang Yao
Department of Trauma and Orthopaedic, Ningbo No. 2 Hospital, Ningbo, Zhejiang, China.
Front Med (Lausanne). 2024 Jun 28;11:1396746. doi: 10.3389/fmed.2024.1396746. eCollection 2024.
We aimed to elucidate the causal relationship between plasma metabolites and the vulnerability to Osteoarthritis (OA), encompassing both hip OA and knee OA.
We conducted a two-way two-sample Mendelian randomization (MR) analysis to investigate the association of 1,400 plasma metabolites with OA. The Inverse Variance Weighted (IVW) model served as the primary two-sample MR Analysis method, with supplementary analysis using the Weighted Median (WM) and MR Egger methods. To ensure the robustness of our findings, sensitivity analyses were performed, incorporating Cochran's Q test, MR-Egger intercept test, MR-PRESSO, and Leave-One-Out analyses. To validate the identified metabolites, we utilized the Steiger test and linkage disequilibrium score regression.
A total of 94 plasma metabolites were associated with osteoarthritis, with 60 associated with hip OA and 106 associated with knee OA. IVW analysis revealed that tryptophan levels showed the strongest positive association with hip OA (OR [95% CI]: 1.119 [1.024, 1.223]), while X-24757 levels exhibited the highest positive association with knee osteoarthritis (OR [95% CI]: 1.095 [1.032, 1.162]). Ethylparaben sulfate levels were found to have the greatest positive association with hip OA (OR [95% CI]: 1.118 [1.015, 1.231]). Notably, the plasma metabolite X-2475 showed a strong robust random effect across all three types of osteoarthritis. Metabolic pathway analysis revealed that the pathogenesis of osteoarthritis in the hip was mediated by acetylarginine, specifically in four important metabolic pathways: ethanol degradation ( = 0.044), amino sugar metabolism ( = 0.090), fatty acid biosynthesis ( = 0.095), and aspartate metabolism ( = 0.097816).
There is a significant association between tryptophan levels and the risk of hip OA, as well as X-24757 levels and the risk of knee osteoarthritis. Additionally, X-24757 levels are also linked to the risk of hip OA. Moreover, this study has identified four crucial metabolic pathways in hip osteoarthritis, which are all regulated by acetylarginine. These findings provide valuable insights into potential biomarkers for OA and highlight potential pathways for its prevention and clinical intervention.
我们旨在阐明血浆代谢物与骨关节炎（OA）易感性之间的因果关系，包括髋骨关节炎和膝骨关节炎。
我们进行了双向两样本孟德尔随机化（MR）分析，以研究1400种血浆代谢物与OA的关联。逆方差加权（IVW）模型作为主要的两样本MR分析方法，并使用加权中位数（WM）和MR Egger方法进行补充分析。为确保研究结果的稳健性，我们进行了敏感性分析，包括Cochran's Q检验、MR-Egger截距检验、MR-PRESSO和留一法分析。为验证所鉴定的代谢物，我们使用了Steiger检验和连锁不平衡评分回归。
共有94种血浆代谢物与骨关节炎相关，其中60种与髋骨关节炎相关，106种与膝骨关节炎相关。IVW分析显示，色氨酸水平与髋骨关节炎呈最强正相关（OR [95% CI]：1.119 [1.024, 1.223]），而X-24757水平与膝骨关节炎呈最高正相关（OR [95% CI]：1.095 [1.032, 1.162]）。发现硫酸对羟基苯甲酸乙酯水平与髋骨关节炎呈最大正相关（OR [95% CI]：1.118 [1.015, 1.231]）。值得注意的是，血浆代谢物X-2475在所有三种类型的骨关节炎中均显示出强大的稳健随机效应。代谢途径分析表明，髋部骨关节炎的发病机制由乙酰精氨酸介导，具体涉及四个重要代谢途径：乙醇降解（ = 0.044）、氨基糖代谢（ = 0.090）、脂肪酸生物合成（ = 0.095）和天冬氨酸代谢（ = 0.097816）。
色氨酸水平与髋骨关节炎风险、X-24757水平与膝骨关节炎风险之间存在显著关联。此外，X-24757水平也与髋骨关节炎风险相关。此外，本研究确定了髋部骨关节炎的四个关键代谢途径，这些途径均由乙酰精氨酸调节。这些发现为OA的潜在生物标志物提供了有价值的见解，并突出了其预防和临床干预的潜在途径。
