免疫细胞、代谢产物与骨关节炎的因果关联的孟德尔随机化研究OA

Objective To investigate the causal associations between immune cells,metabolites and osteoarthritis(OA)by mediation Mendelian randomization(MMR),and to provide new scientific insights for the study of OA pathogenesis and clinical treatment.Methods Based on the publicly available Genome-Wide Association Study database,a comprehensive analysis was conducted involving 731 types of immune cells 1400 metabolites,and OA-related genetic data.A systematic evaluation of causal relationships among these three factors was performed using two-sample methods and MMR approaches.Results Mendelian randomization analysis results indicated a clear causal relationship between HLA DR expression on CD14+CD16+monocytes,CD8 expression on TD CD8br T cells,CD4+activated Treg cells,and OA,as well as significant causal links among 20 metabolites and OA.MMR revealed that N-acetylmethionine mediates the reduction of OA risk through CD8 expression on TD CD8br T cells,while 4-hydroxychlorophenol and the glycine/serine ratio both mediate this risk reduction via CD4+activated Treg cells.(S)-3-hydroxybutyryl carnitine mediates OA risk reduction through HLA DR CD14+CD16+monocytes,with no heterogeneity or level heterogeneity observed during the study(P>0.05).Conclusion This study employed the MMR method to demonstrate that metabolites can mediate the influence of immune cells on the pathogenesis of OA.