Lin Jiannan, Lu Shuwen, Zhao Xiaoyu
Department of Pediatrics, Jiaxing Second Hospital, Jiaxing, 314000, China.
Hereditas. 2025 Feb 1;162(1):12. doi: 10.1186/s41065-025-00376-w.
With the development of the economy, the number of obese patients has been increasing annually worldwide. The proportion of asthma patients associated with obesity is also gradually rising. However, the pathogenesis of obesity-related asthma remains incompletely understood, and conventional pharmacological treatments generally show limited efficacy.
This study aims to explore the causal relationship between obesity and allergic asthma, elucidate the pathogenesis of obesity-related asthma, and identify the plasma proteins involved in its development, providing new insights for clinical interventions.
In this study, we employed a two-step approach for mediation Mendelian randomization (MR) analysis, utilizing stringent selection criteria to identify instrumental variables (IVs). This approach was used to assess the causal impact of obesity on allergic asthma and to validate the plasma proteins identified as mediating factors. We further explored the functions and enriched pathways of the mediating proteins using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. Finally, we conducted drug-targeted MR analysis to evaluate the potential of each mediator plasma proteins as a drug target gene. If significant heterogeneity remained among the IVs, we applied the weighted median method as the primary analytical tool. Otherwise, we utilized the inverse variance weighted (IVW) method as the main analytical approach. Additionally, we conducted various sensitivity analyses and statistical tests to further illustrate the robustness of the observed associations.
The research findings indicate a causal relationship between obesity and allergic asthma. Plasma proteins such as TPST1, ROR1, and DAPK1 mediate this relationship, with TPST1 accounting for over 10% of the mediation effect. GO and KEGG analyses show that the genes corresponding to these mediator proteins are primarily enriched in pathways related to responses to stimuli, carbohydrate synthesis and metabolism, regulation of certain protein activities, and synaptic connections. The drug-targeted MR analysis suggests that SIGLEC12, BOLA1, HOMER2, and TPST1 all have the potential to be drug target genes.
This study suggests that obese patients defined by BMI may promote the development of allergic asthma by influencing the expression of plasma proteins such as TPST1, ROR1, and DAPK1. Furthermore, some of these plasma proteins, including TPST1, could potentially serve as therapeutic targets for treating allergic asthma in these patients. However, further research is needed to explore their therapeutic potential and the mechanisms underlying their effects.
Not applicable.
随着经济的发展，全球肥胖患者数量逐年增加。与肥胖相关的哮喘患者比例也在逐渐上升。然而，肥胖相关性哮喘的发病机制仍未完全明确，传统药物治疗通常疗效有限。
本研究旨在探讨肥胖与过敏性哮喘之间的因果关系，阐明肥胖相关性哮喘的发病机制，并确定参与其发病过程的血浆蛋白，为临床干预提供新的见解。
在本研究中，我们采用两步法进行中介孟德尔随机化（MR）分析，利用严格的选择标准确定工具变量（IVs）。该方法用于评估肥胖对过敏性哮喘的因果影响，并验证被确定为中介因素的血浆蛋白。我们使用基因本体论（GO）和京都基因与基因组百科全书（KEGG）分析进一步探索中介蛋白的功能和富集途径。最后，我们进行药物靶向MR分析，以评估每种中介血浆蛋白作为药物靶基因的潜力。如果IVs之间仍存在显著异质性，我们将加权中位数法作为主要分析工具。否则，我们使用逆方差加权（IVW）法作为主要分析方法。此外，我们进行了各种敏感性分析和统计检验，以进一步说明观察到的关联的稳健性。
研究结果表明肥胖与过敏性哮喘之间存在因果关系。血浆蛋白如TPST1、ROR1和DAPK1介导了这种关系，其中TPST1占中介效应的10%以上。GO和KEGG分析表明，这些中介蛋白对应的基因主要富集在与刺激反应、碳水化合物合成与代谢、某些蛋白质活性调节和突触连接相关的途径中。药物靶向MR分析表明，SIGLEC12、BOLA1、HOMER2和TPST1都有潜力成为药物靶基因。
本研究表明，以BMI定义的肥胖患者可能通过影响TPST1、ROR1和DAPK1等血浆蛋白的表达来促进过敏性哮喘的发展。此外，这些血浆蛋白中的一些，包括TPST1，有可能成为治疗这些患者过敏性哮喘的治疗靶点。然而，需要进一步研究来探索它们的治疗潜力及其作用的潜在机制。
不适用。
