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中华损伤与修复杂志(电子版) ›› 2024, Vol. 19 ›› Issue (06) : 467 -473. doi: 10.3877/cma.j.issn.1673-9450.2024.06.003

论著

膝骨关节炎相关炎症因子与血浆代谢物间的因果关系及中介效应
王振宇1, 张洪美1,(), 荆琳1, 何名江1, 闫奇1   
  1. 1.100102 北京,中国中医科学院望京医院骨关节一科
  • 收稿日期:2024-09-18 出版日期:2024-12-01
  • 通信作者: 张洪美
  • 基金资助:
    北京市科委科技计划(Z201110005520058)中国中医科学院科技创新工程(C1201A02005)

Causal relationship and mediating effect between knee osteoarthritis related inflammatory factors and plasma metabolites

Zhenyu Wang1, Hongmei Zhang1,(), Lin Jing1, Mingjiang He1, Qi Yan1   

  1. 1.The First Department of Bone and Joint Diseases, Wangjing Hospital, China Academy of Chinese Medical Sciences,Beijing 100102, China
  • Received:2024-09-18 Published:2024-12-01
  • Corresponding author: Hongmei Zhang
引用本文:

王振宇, 张洪美, 荆琳, 何名江, 闫奇. 膝骨关节炎相关炎症因子与血浆代谢物间的因果关系及中介效应[J]. 中华损伤与修复杂志(电子版), 2024, 19(06): 467-473.

Zhenyu Wang, Hongmei Zhang, Lin Jing, Mingjiang He, Qi Yan. Causal relationship and mediating effect between knee osteoarthritis related inflammatory factors and plasma metabolites[J]. Chinese Journal of Injury Repair and Wound Healing(Electronic Edition), 2024, 19(06): 467-473.

目的

采用孟德尔随机化(MR)系统评估炎症因子、血浆代谢物与膝骨关节炎(KOA)间的因果关系及血浆代谢物在炎症因子介导的KOA 中的中介效应。

方法

自全基因组关联分析(GWAS)公共数据库获取91 种炎症因子、1 400 种血浆代谢物和KOA 的GWAS 数据。 使用两样本MR 分析,对炎症因子、代谢物与KOA 和KOA 相关炎症因子与代谢物间的因果关系进行评估,对代谢物在炎症因子介导的KOA 中的中介效应进行估计。

结果

2 种炎症因子(CD5、FGF-5)、65 种血浆代谢物与KOA 存在显著因果关系。 中介分析发现N-乙酰基-1-甲基-L-组氨酸在FGF-5 与KOA 的因果关系中存在3.7%的中介效应比。

结论

多种炎症因子及代谢物与KOA 存在因果关系,代谢对KOA 的影响应予重视。 T 细胞在预防KOA 中有重要作用,从遗传学层面可解释富白细胞富血小板血浆的抗炎作用。 FGF 通路在预防预防KOA 方面有潜力,为未来PRP 组分研究提供了参考。

Objective

To evaluate the causal relationship between inflammatory factors, plasma metabolites and knee osteoarthritis (KOA) and the mediating effect of plasma metabolites in inflammatory factor-mediated KOA using Mendelian randomization (MR) system.

Methods

The genome-wide association study (GWAS) data of 91 inflammatory factors, 1 400 plasma metabolites and KOA were obtained from the public GWAS database.Two-sample MR analysis was used to evaluate the causal relationship between inflammatory factors, metabolites and KOA and KOA-related inflammatory factors and metabolites, and then the mediating effect of metabolites in inflammatory factor-mediated KOA was estimated.

Results

2 inflammatory factors (CD5, FGF-5) and 65 plasma metabolites were found to have significant causal relationships with KOA.Mediation analysis found that N-acetyl-1-methylhistidine had a 3.7% mediating effect ratio in the causal relationship between FGF-5 and KOA.

Conclusion

A variety of inflammatory factors and metabolites have a causal relationship with KOA, and the effect of metabolism on KOA should be paid attention to.The role of T cells in the prevention of KOA is confirmed, and the anti-inflammatory effect of leukocyte-rich platelet-rich plasma is explained from the genetic level.The potential of FGF pathway to prevent KOA is identified, which provides a reference for future studies of PRP components.

图1 炎症因子与KOA 的因果关系。 以下三者均为暴露指标,膝骨关节炎为结局指标:eukaryotic translation initiation factor 4E-binding protein 1 为真核翻译起始因子4E 结合蛋白1;T-cell surface glycoprotein CD5 为T 细胞表面糖蛋白CD5;fibroblast growth factor 5 为成纤维细胞生长因子5
表1 2 个炎症因子与KOA 因果关系的水平多效性检验和异质性检验结果
图2 2 种KOA 相关炎症因子的留一法分析结果。 A 示CD-5 与KOA 间MR 分析留一法分析结果;B 示FGF-5与KOA 间MR 分析留一法分析结果
图3 血浆代谢物与KOA 的因果关系(IVW 法);其中血浆代谢物为暴露指标,膝骨关节炎为结局指标,仅展示P<0.01 及存在中介效应的代谢物结果
图4 CD5 与血浆代谢物的因果关系(IVW 法);CD5 为暴露指标,血浆代谢物为结局指标,仅展示P<0.01 的结果
图5 FGF-5 与血浆代谢物的因果关系(IVW 法);FGF-5 为暴露指标,血浆代谢物为结局指标,仅展示P<0.01 及存在中介效应的结果
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