探索炎性细胞因子与膝关节骨关节炎之间的因果关系：一项两样本孟德尔随机化研究

Exploring causal correlations between inflammatory cytokines and knee osteoarthritis: a two-sample Mendelian randomization.

作者信息

Zhang Jiayu, Li Kexuan, Qiu Xiuyue

机构信息

Nursing School, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China.

出版信息

Front Immunol. 2024 Apr 18;15:1362012. doi: 10.3389/fimmu.2024.1362012. eCollection 2024.

DOI:10.3389/fimmu.2024.1362012

PMID:38698846

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11063282/

Abstract

OBJECTIVES

Knee osteoarthritis (KOA) and certain inflammatory cytokines (such as interleukin 1 [IL-1] and tumor necrosis factor alpha [TNF-a]) are related; however, the causal relationship remains unclear. Here, we aimed to assess the causal relationship between 41 inflammatory cytokines and KOA using Mendelian randomization (MR).

METHODS

Two-sample bidirectional MR was performed using genetic variation data for 41 inflammatory cytokines that were obtained from European Genome-Wide Association Study (GWAS) data (n=8293). KOA-related genetic association data were also obtained from European GWAS data (n=40,3124). Inverse variance weighting (IVW), MR, heterogeneity, sensitivity, and multiple validation analyses were performed.

RESULTS

Granulocyte colony-stimulating factor (G-CSF) or colony-stimulating factor 3 (CSF-3) levels were negatively associated with the risk of developing KOA (OR: 0.93, 95%CI:0.89-0.99, =0.015). Additionally, macrophage inflammatory protein-1 alpha (MIP-1A/CCL3) was a consequence of KOA (OR: 0.72, 95%CI:0.54-0.97, =0.032). No causal relationship was evident between other inflammatory cytokines and KOA development.

CONCLUSION

This study suggests that certain inflammatory cytokines may be associated with KOA etiology. G-CSF exerts an upstream influence on KOA development, whereas MIP-1A (CCL-3) acts as a downstream factor.

摘要

目的

膝关节骨关节炎（KOA）与某些炎性细胞因子（如白细胞介素1 [IL-1]和肿瘤坏死因子α [TNF-α]）相关；然而，因果关系仍不明确。在此，我们旨在使用孟德尔随机化（MR）评估41种炎性细胞因子与KOA之间的因果关系。

方法

使用从欧洲全基因组关联研究（GWAS）数据（n = 8293）中获得的41种炎性细胞因子的基因变异数据进行两样本双向MR。KOA相关的基因关联数据也从欧洲GWAS数据（n = 403124）中获得。进行了逆方差加权（IVW）、MR、异质性、敏感性和多重验证分析。

结果

粒细胞集落刺激因子（G-CSF）或集落刺激因子3（CSF-3）水平与发生KOA的风险呈负相关（OR：0.93，95%CI：0.89 - 0.99，P = 0.015）。此外，巨噬细胞炎性蛋白-1α（MIP-1A/CCL3）是KOA的一个结果（OR：0.72，95%CI：0.54 - 0.97，P = 0.032）。其他炎性细胞因子与KOA发展之间未发现明显的因果关系。