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| 两样本孟德尔随机化研究炎症因子与骨质疏松症的因果关联 |
| Causal association between inflammatory factors and osteoporosis under the perspective of osteoimmunology: A two-sample Mendelian randomization study |
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| DOI：10.3969/j.issn.1006-7108.2025.01.011 |
| 中文关键词: 骨免疫 炎症因子 骨质疏松症 孟德尔随机化 药物靶点 |
| 英文关键词:osteoimmunology inflammatory factors osteoporosis Mendelian randomization drug targets |
| 基金项目:江苏省科技计划专项资金（基础研究计划自然科学基金）（BK20220468）；江苏省研究生科研与实践创新计划项目（KYCX24_2332，KYCX24_2251，KYCX23_2208） |
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| 中文摘要: |
| 目的 评估炎症因子与骨质疏松症(osteoporosis，OP)之间的因果关系。方法 从GWAScatalog数据库中获取41个炎症因子和骨密度(bone mineral density，BMD)的GWAS数据，芬兰数据库中获取OP的GWAS数据。采用逆方差加权法(IVW)、MR-Egger回归法(MER)、加权中位数法(WME)、简单中位数法和加权中值方法进行两样本孟德尔随机化分析，并以IVW法为主要分析方法。再进行敏感性分析以检验结果的可靠性，留一法评估单核苷酸多态性对结果的影响。最后进行药物预测和分子对接进一步验证炎症因子的药理价值。结果 研究表明炎症因子与OP和BMD之间存在因果关系。其中肿瘤坏死因子相关的凋亡诱导配体(TRAIL)和单核细胞趋化蛋白1(MCP-1/MCAF)与OP发生风险呈正相关；肿瘤坏死因子β(TNF-β)与0～15岁人群的BMD呈负相关；白细胞介素7(IL-7)与15～30岁人群的BMD呈负相关；肝细胞生长因子(HGF)与30～45岁人群的BMD呈负相关；巨噬细胞炎性蛋白1α(MIP-1α)和巨噬细胞集落刺激因子(M-CSF)与60岁以上人群的BMD呈负相关；MIP-1α与全年龄段人群的BMD呈负相关。此外，分子对接证明了药物与蛋白质的良好结合，进一步证实了这些靶点的药理价值。结论 通过孟德尔随机化方法全面评估了41种炎症因子对OP和BMD的因果效应，表明炎症因子与OP和BMD之间存在因果关联，提示OP患者可以在疾病早期通过干预炎症因子进而干预OP的发生发展过程。 |
| 英文摘要: |
| Objective To assess the causal relationship between inflammatory factors and osteoporosis (OP). Methods GWAS data for 41 inflammatory factors and bone mineral density (BMD) were obtained from the GWAS catalog database and OP GWAS data were obtained from the Finnish database. Mendelian randomization analysis was conducted using inverse variance weighted method (IVW), MR-Egger regression (MER), weighted median method (WME), simple median method, and weighted mode method. IVW was primarily employed for analysis. Sensitivity analysis was performed to assess the reliability of results. The impact of single nucleotide polymorphisms on the outcome was evaluated using sleave-one-out analysis. Finally, drug prediction and molecular docking were conducted to further validate the pharmacological value of inflammatory factors. Results The study indicated a causal relationship between inflammatory factors and OP and BMD. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and monocyte chemoattractant protein-1 (MCP-1/MCAF) were positively associated with the risk of developing OP. Tumor necrosis factor β (TNF-β) was negatively associated with BMD in individuals aged 0-15. Interleukin-7 (IL-7) was negatively associated with BMD in individuals aged 15-30. Hepatocyte growth factor (HGF) was negatively associated with BMD in individuals aged 30-45. Macrophage inflammatory protein 1α (MIP-1α) and macrophage colony-stimulating factor (M-CSF) were negatively associated with BMD in individuals aged over 60. MIP-1α was negatively associated with BMD across all age groups. Additionally, molecular docking confirmed the favorable binding between the drugs and proteins, further validating the pharmacological value of these targets. Conclusion The MR approach comprehensively evaluates the causal effects of 41 inflammatory factors on OP and BMD, indicating a causal association between inflammatory factors and OP and BMD. This suggests that intervention in inflammatory factors in the early stages of the disease could influence the development and progression of OP. |
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