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| 孟德尔随机化研究炎症细胞因子与RANK因果关联 |
| Causal association between inflammatory cytokines and RANK: Evidence from Mendelian randomization studies |
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| DOI：10.3969/j.issn.1006-7108.2026.02.009 |
| 中文关键词: 孟德尔随机化 骨质疏松症 核因子κB受体活化因子 炎症细胞因子 骨代谢 因果关联 |
| 英文关键词:Mendelian randomization osteoporosis RANK inflammatory cytokines bone metabolism causal associations |
| 基金项目:贵州省卫生健康委科学技术基金（gzwkj2025-364）;北京积水潭医院贵州医院院内基金[JGYYK(2025)16号]；贵中医科余（2025）48号 |
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| 中文摘要: |
| 目的 明确哪些炎症细胞因子与核因子κB受体活化因子（receptor activator of nuclear factor kappa-B，RANK）之间存在因果关联。方法 提取全基因组关联研究公开数据库中炎症细胞因子和RANK的相关数据。采用逆方差加权法、MR Egger回归、加权中值法、简单模式法、增强模式等进行分析，并应用敏感性分析验证结果强度。结果 ?CCL20?（OR=7.31，95% CI：2.61～20.52，P＜0.001）与 ?MMP-1?（OR=1.93，95% CI：1.21～3.09，P=0.006）均与RANK呈显著正向关联。RANK与 ?FGF-23? (OR=0.956 8，95% CI：0.924 9～0.989 8)、?IL-12β? (OR=0.971 2，95% CI：0.947 3～0.995 6)、?TSLP? (OR=0.970 0，95% CI：0.941 8～0.999 1) 存在显著负向关联（P＜0.05）。RANK与 ?MMP-10? (OR=1.0270，95% CI：1.001 6～1.052 9)、?OSM? (OR=1.036 3，95% CI：1.010 6～1.062 5)、?TGF-α ?(OR=1.031 9，95% CI：1.006 6～1.057 8) 存在显著正向关联（P＜0.05）。结论 CCL20和MMP-1的水平升高均与RANK的增加显著正相关。RANK 与?FGF-23、IL-12 β和?TSLP存在负相关，RANK升高时，这些因子的水平降低。RANK与MMP-10、OSM和TGF-α?水平升高存在显著正相关，RANK升高导致这些因子水平增加。 |
| 英文摘要: |
| Objective To identify causal association between specific inflammatory cytokines and RANK. Methods Data related to inflammatory cytokines and RANK were extracted from publicly available genome-wide association study databases. Inverse variance-weighted (IVW) method, MR Egger regression, weighted median method, simple mode, enhanced mode, and other analyses were conducted. Sensitivity analysis was applied to verify the robustness of the results. Results CCL20 (OR=7.31, 95% CI: 2.61-20.52, P<0.001) and MMP-1 (OR=1.93, 95% CI: 1.21-3.09, P=0.006) showed significant positive associations with RANK. Significant negative associations were observed between RANK and FGF-23 (OR=0.956 8, 95% CI: 0.924 9–0.989 8), IL-12β (OR=0.971 2, 95% CI: 0.947 3–0.995 6), and TSLP (OR=0.970 0, 95% CI:0.941 8–0.999 1, P <0.05). Additionally, RANK exhibited significant positive associations with MMP-10 (OR=1.027 0, 95% CI: 1.001 6–1.052 9), OSM (OR=1.036 3, 95% CI: 1.010 6–1.062 5), and TGF-α (OR=1.031 9, 95% CI: 1.006 6–1.057 8, P<0.05). Conclusion Elevated levels of CCL20 and MMP-1 are significantly positively associated with increased RANK. RANK negatively correlates with FGF-23, IL-12β, and TSLP, suggesting decreased levels of these factors with increased RANK. There are significant positive correlations between RANK and elevated levels of MMP-10, OSM, and TGF-α, indicating increased levels of these factors with higher RANK. |
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