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

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

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、1400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,1400 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.