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多种细胞因子与哮喘之间的因果关系:双向两样本孟德尔随机化分析

Causality between various cytokines and asthma: a bidirectional two-sample Mendelian randomization analysis.

作者信息

Zheng Yansen, Chen Qi, Shi Xiaqing, Lei Lei, Wang Donglin

机构信息

Medical School, Huanghe Science and Technology College, Zhengzhou, China.

Jice Medical Institute, Xi'an, Shaanxi, China.

出版信息

Front Med (Lausanne). 2024 Aug 8;11:1447673. doi: 10.3389/fmed.2024.1447673. eCollection 2024.

Abstract

BACKGROUND

Many studies have shown that cytokines play an important role in the pathogenesis of asthma, but their biological effects on asthma remain unclear. The Mendelian randomization (MR) method was used to evaluate the causal relationship between various cytokines [such as interleukins (ILs), interferons (IFNs), tumor necrosis factors (TNFs), colony-stimulating factors (CSFs), transforming growth factor (TGF), etc.,] and asthma.

METHODS

In this study, inverse variance weighting was used to evaluate the causal relationship between asthma and cytokines. In addition, the reliability of the results is ensured by multiple methods such as MR-Egger, weighted median, MR-Raps, MR-Presso, and RadialMR, as well as sensitivity analysis.

RESULTS

The results showed that none of the 11 cytokines was associated with the risk of asthma. In contrast, asthma can increase levels of IL-5 [odds ratio (OR) = 1.112, 95% confidence interval (CI): 1.009-1.224, = 0.032] and IL-9 (OR = 1.111, 95% CI: 1.013-1.219, = 0.025).

CONCLUSION

Genetically predicted asthma was positively associated with elevated levels of IL-5 and IL-9, indicating the downstream effects of IL-5 and IL-9 on asthma. Medical treatments can thus be designed to target IL-5 and IL-9 to prevent asthma exacerbations.

摘要

背景

许多研究表明,细胞因子在哮喘发病机制中起重要作用,但其对哮喘的生物学影响仍不明确。采用孟德尔随机化(MR)方法评估多种细胞因子[如白细胞介素(ILs)、干扰素(IFNs)、肿瘤坏死因子(TNFs)、集落刺激因子(CSFs)、转化生长因子(TGF)等]与哮喘之间的因果关系。

方法

本研究采用逆方差加权法评估哮喘与细胞因子之间的因果关系。此外,通过MR-Egger、加权中位数、MR-Raps、MR-Presso和RadialMR等多种方法以及敏感性分析来确保结果的可靠性。

结果

结果显示,11种细胞因子均与哮喘风险无关。相反,哮喘可使IL-5水平升高[比值比(OR)=1.112,95%置信区间(CI):1.009 - 1.224,P = 0.032]和IL-9水平升高(OR = 1.111,95%CI:1.013 - 1.219,P = 0.025)。

结论

基因预测的哮喘与IL-5和IL-9水平升高呈正相关,表明IL-5和IL-9对哮喘具有下游效应。因此,可以设计针对IL-5和IL-9的医学治疗方法来预防哮喘发作。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d16/11338859/d500c5e14e34/fmed-11-1447673-g001.jpg

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