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儿童哮喘与阻塞性睡眠呼吸暂停的孟德尔随机化分析及分子机制研究

Mendelian randomization analysis and molecular mechanism study of childhood asthma and obstructive sleep apnea.

作者信息

Wang Xinyu, Zhang Lin, Chen Hao, Tian Ting, Wu Lulu, Huang Yuping, Cao Qian, Zhuang Lili, Zhou Guoping

机构信息

Department of Pediatrics, The First Affiliated Hospital of Nanjing Medical University, Guangzhou Road 300, Nanjing, 210029, China.

Department of Children's Health Care, The First Affiliated Hospital of Nanjing Medical University, Guangzhou Road 300, Nanjing, 210029, China.

出版信息

Hum Genet. 2025 Apr;144(4):443-461. doi: 10.1007/s00439-025-02734-0. Epub 2025 Mar 3.

Abstract

Childhood asthma is a common chronic respiratory disorder influenced by various factors, and obstructive sleep apnea (OSA) has emerged as a significant comorbidity. This study sought to investigate the underlying molecular mechanisms of the comorbidity between childhood asthma and OSA through Mendelian randomization (MR) analysis. Gene expression and genotype data were analyzed from public databases, and single nucleotide polymorphisms (SNPs) related to both diseases were identified. Our research findings unveiled 242 gene pairs associated with childhood asthma and 350 gene pairs related to OSA. Among them, the three hub genes, namely LRP3, BAK1, and CLIC4, exhibited significant expression alterations in both diseases. These hub genes participate in multiple signal transduction pathways and exhibit a remarkable correlation with the infiltration of immune cells, suggesting that they exert a vital role in modulating the immune microenvironment. Further analyses, encompassing gene set enrichment and transcriptional regulation, emphasized the complex interplay between these genes and non-coding RNAs as well as transcription factors. Our study results stressed the bidirectional relationship between childhood asthma and OSA and accentuated the significance of early identification and targeted intervention. This study identified potential therapeutic targets and laid a foundation for formulating treatment strategies aimed at improving the conditions of children with these interrelated diseases.

摘要

儿童哮喘是一种受多种因素影响的常见慢性呼吸系统疾病,而阻塞性睡眠呼吸暂停(OSA)已成为一种重要的合并症。本研究旨在通过孟德尔随机化(MR)分析探讨儿童哮喘与OSA合并症的潜在分子机制。从公共数据库中分析基因表达和基因型数据,并鉴定与这两种疾病相关的单核苷酸多态性(SNP)。我们的研究结果揭示了242个与儿童哮喘相关的基因对和350个与OSA相关的基因对。其中,三个枢纽基因,即低密度脂蛋白受体相关蛋白3(LRP3)、凋亡相关蛋白激酶1(BAK1)和氯离子细胞内通道蛋白4(CLIC4),在这两种疾病中均表现出显著的表达改变。这些枢纽基因参与多种信号转导途径,并与免疫细胞浸润显著相关,表明它们在调节免疫微环境中发挥着至关重要的作用。进一步的分析,包括基因集富集和转录调控,强调了这些基因与非编码RNA以及转录因子之间的复杂相互作用。我们的研究结果强调了儿童哮喘与OSA之间的双向关系,并突出了早期识别和靶向干预的重要性。本研究确定了潜在的治疗靶点,为制定旨在改善患有这些相关疾病儿童状况的治疗策略奠定了基础。

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