循环炎症蛋白作为哮喘的病因驱动因素和治疗靶点:来自遗传和通路分析的见解。

IF 1.3 4区 医学 Q3 ALLERGY
Yiyan Miao, Haihua Chen, Qishu Wei, Kun Yan, Praise Audax Rukonge, Zhe Zhang, Guiping Yu
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引用次数: 0

摘要

背景:慢性炎症在哮喘发病中起核心作用,但特异性循环炎症蛋白的因果作用尚不清楚。在这里,我们整合了遗传和基于通路的分析来识别可能驱动哮喘发展并作为治疗靶点的炎症蛋白。方法:我们使用来自180个蛋白质数量性状位点(pqtl)的遗传锚定工具变量,使用大规模GWAS数据集评估91种循环炎症蛋白对哮喘风险的因果影响。通过多效性和异质性检验评估分析稳健性。进行功能富集和基于文献的途径分析以支持生物学合理性并验证研究结果。结果:4种蛋白对哮喘有显著的因果影响:CCL19和LIFR具有保护作用(OR = 0.89和0.91,p≤6.80 e -03),而ARTN和IL6与哮喘风险增加相关(OR = 1.15和1.18,p≤1.1E-04)。我们还确定了哮喘对11种细胞因子的反向因果效应,包括MMP10、TGFB1、IL33和IL18R1。这些蛋白大多富集于细胞因子信号通路和免疫应答相关通路(p < 0.001)。所有确定的蛋白质都有先前的文献支持,将它们与哮喘或气道炎症联系起来。结论:我们的研究结果强调了循环炎症蛋白的一个子集,它们可能是哮喘发病的原因,并可能作为治疗干预的有希望的靶点。这些结果为哮喘的免疫学机制提供了新的见解,并支持遗传因果推理在目标优先排序中的应用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Circulating inflammatory proteins as causal drivers and therapeutic targets in asthma: insights from genetic and pathway-based analyses.

Objective: To identify circulating inflammatory proteins with potential causal roles in asthma development through integrated genetic and pathway-based analyses, and to evaluate their potential as therapeutic targets.

Methods: We used genetically anchored instrumental variables from 180 protein quantitative trait loci (pQTLs) to assess the causal effects of 91 circulating inflammatory proteins on asthma risk, using large-scale GWAS datasets. Analytical robustness was evaluated through pleiotropy and heterogeneity testing. Functional enrichment and literature-based pathway analyses were performed to support biological plausibility and validate findings.

Results: Four proteins showed significant causal effects on asthma: CCL19 and LIFR were protective (OR = 0.89 and 0.91, p ≤ 6.8E-03), while ARTN and IL6 were associated with increased risk (OR = 1.15 and 1.18, p ≤ 1.1E-04). We also identified reverse causal effects of asthma on 11 cytokines, including MMP10, TGFB1, IL33, and IL18R1. Most of these proteins were enriched in pathways related to cytokine signaling and immune response (p < 0.001). All identified proteins had prior literature support linking them to asthma or airway inflammation.

Conclusions: Our findings highlight a subset of circulating inflammatory proteins that are likely causal in asthma pathogenesis and may serve as promising targets for therapeutic intervention. These results offer novel insights into the immunological mechanisms underlying asthma and support the utility of genetic causal inference in target prioritization.

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来源期刊
Journal of Asthma
Journal of Asthma 医学-过敏
CiteScore
4.00
自引率
5.30%
发文量
158
审稿时长
3-8 weeks
期刊介绍: Providing an authoritative open forum on asthma and related conditions, Journal of Asthma publishes clinical research around such topics as asthma management, critical and long-term care, preventative measures, environmental counselling, and patient education.
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