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循环炎症细胞因子与疝气风险之间的因果关系:一项双向孟德尔随机化研究

Causal relationship between circulating inflammatory cytokines and the risk of hernia: a bidirectional Mendelian randomization study.

作者信息

Qi Yaqin, Li Changjiu, Gao Xingyue, Zhang Fangjie

机构信息

The Fourth School of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou First People's Hospital, Hangzhou, China.

Department of Urology, Affiliated Hangzhou First People's Hospital, School of Medicine, Westlake University, Hangzhou, China.

出版信息

J Int Med Res. 2025 Feb;53(2):3000605251315923. doi: 10.1177/03000605251315923.

Abstract

OBJECTIVE

Observational studies suggest a link between hernia and inflammatory cytokines, but randomized trials are limited by ethical and cost constraints. In this study, we used bidirectional Mendelian randomization (MR) to investigate the causal relationship between inflammatory cytokines and five types of hernia, aiming to inform preventive and therapeutic strategies.

METHODS

We selected 41 inflammatory factors and five types of hernia as instrumental variables, using data from the IEU Open GWAS database including individuals of European descent. The primary analysis used the inverse variance weighted method with false discovery rate (FDR) adjustment. Additional MR methods and sensitivity analyses ensured robustness. Reverse MR was used to assess potential reverse causality.

RESULTS

After FDR adjustment, stem cell growth factor beta (SCGFb) was causally associated with diaphragmatic hernia (odds ratio = 0.884, 95% confidence interval: 0.819-0.955). Reverse MR indicated that diaphragmatic hernia may increase interferon gamma-induced protein 10 (IP10) and monokine induced by interferon-gamma (MIG), and ventral hernia may elevate macrophage inflammatory protein-1b (MIP1b). Sensitivity analyses confirmed robustness.

CONCLUSION

SCGFb may protect against diaphragmatic hernia, and IP10, MIG, and MIP1b are involved in hernia development, suggesting the therapeutic potential of targeting these cytokines. Further studies are needed.

摘要

目的

观察性研究表明疝气与炎性细胞因子之间存在联系,但随机试验受到伦理和成本限制。在本研究中,我们使用双向孟德尔随机化(MR)来研究炎性细胞因子与五种疝气类型之间的因果关系,旨在为预防和治疗策略提供依据。

方法

我们选择41种炎性因子和五种疝气类型作为工具变量,使用来自IEU Open GWAS数据库的数据,其中包括欧洲血统的个体。主要分析采用逆方差加权法并进行错误发现率(FDR)调整。额外的MR方法和敏感性分析确保了稳健性。反向MR用于评估潜在的反向因果关系。

结果

经过FDR调整后,干细胞生长因子β(SCGFb)与膈疝存在因果关联(优势比=0.884,95%置信区间:0.819-0.955)。反向MR表明,膈疝可能会增加干扰素γ诱导蛋白10(IP10)和干扰素γ诱导的单核因子(MIG),腹疝可能会升高巨噬细胞炎性蛋白-1b(MIP1b)。敏感性分析证实了结果的稳健性。

结论

SCGFb可能对膈疝具有保护作用,IP10、MIG和MIP1b参与疝气的发生发展,提示靶向这些细胞因子具有治疗潜力。需要进一步研究。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a69d/11831628/a596dde58f43/10.1177_03000605251315923-fig1.jpg

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