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探索炎症性细胞因子和膝关节骨关节炎之间的因果关系:一个两个样本的门德尔随机化

Jiayu Zhang¹, Kexuan Li¹, Xiuyue Qiu¹

¹Nursing School, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China.

Frontiers in immunology

|May 3, 2024

概括

颗粒细胞殖民地刺激因子 (G-CSF) 可能会降低膝关节关节炎 (KOA) 的风险,而巨细胞炎症蛋白-1α (MIP-1A) 似乎是KOA的结果. 这项研究澄清了特定细胞因子和KOA发展之间的因果关系.

科学领域:

遗传学和分子生物学
免疫学免疫学免疫学
类风湿病学类风湿病学

背景情况:

膝关节骨关节炎 (KOA) 是一种具有复杂病因的普遍疾病.
炎症性细胞因子,如互白素-1 (IL-1) 和瘤亡因子-α (TNF-a),都与KOA的发病有关.
具体的炎症性细胞因子和KOA之间的确切因果关系仍然不完全理解.

研究的目的:

研究41种炎症性细胞因子与患膝关节关节炎 (KOA) 的风险之间的因果关系.
在KOA病因学中区分细胞因子的上游和下游影响,使用双向门德尔随机化方法.

主要方法:

进行了一项双样双向孟德尔随机化 (MR) 研究.
41种炎症性细胞因子 (n=8293) 和膝关节骨关节炎 (n=403,124) 的遗传变异数据来自欧洲全基因组协会研究 (GWAS).
使用逆方差加权 (IVW) 和各种敏感性分析来评估因果关系.

主要成果:

颗粒细胞殖民地刺激因子 (G-CSF/CSF-3) 显示出保护作用,与KOA风险负相关 (OR:0.93,95% CI:0.89-0.99,P=0.015).
巨炎性蛋白-1α (MIP-1A/CCL3) 被确定为KOA的结果 (OR:0.72,95%CI:0.54-0.97,P=0.032).
对于其他测试的炎症性细胞因子和KOA,没有发现显著的因果关系.

结论:

某些炎症性细胞因子在膝关节骨关节炎的病因中起作用.
G-CSF (CSF-3) 似乎影响了KOA的发展,可能作为一个上游因素.
建议MIP-1A (CCL-3) 是KOA的下游后果,表明它参与了疾病过程.

关键词:

门德尔的随机化疾病病因疾病病因学遗传变异是一种遗传变异.炎症性细胞因子是炎症性细胞因子.膝盖骨关节炎膝盖骨关节炎

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