Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.
Institute of Epidemiology and Preventive Medicine, National Taiwan University, Taipei, Taiwan.
Thorax. 2020 Sep;75(9):725-734. doi: 10.1136/thoraxjnl-2019-214132. Epub 2020 Jun 30.
Respiratory syncytial virus (RSV) is associated with childhood asthma. Nevertheless, not all children exposed to RSV develop asthma symptoms, possibly because genes modulate the effects of RSV on asthma exacerbations.
The purpose of this study was to identify genes that modulate the effect of RSV latent infection on asthma exacerbations.
We performed a meta-analysis to investigate differentially expressed genes (DEGs) of RSV infection from Gene Expression Omnibus datasets. Expression quantitative trait loci (eQTL) methods were applied to select single nucleotide polymorphisms (SNPs) that were associated with DEGs. Gene-based analysis was used to identify SNPs that were significantly associated with asthma exacerbations in the Taiwanese Consortium of Childhood Asthma Study (TCCAS), and validation was attempted in an independent cohort, the Childhood Asthma Management Program (CAMP). Gene-RSV interaction analyses were performed to investigate the association between the interaction of SNPs and RSV latent infection on asthma exacerbations.
A total of 352 significant DEGs were found by meta-analysis of RSV-related genes. We used 38 123 SNPs related to DEGs to investigate the genetic main effects on asthma exacerbations. We found that eight RSV-related genes ( and ) were significantly associated with asthma exacerbations in TCCAS and also validated in CAMP. In TCCAS, rs7251960 () significantly modulated the effect of RSV latent infection on asthma exacerbations (false-discovery rate <0.05). The rs7251960 variant was associated with mRNA expression in lung tissue (p for trend=1.2×10). mRNA was reduced in nasal mucosa from subjects with asthma exacerbations in two independent datasets.
rs7251960 is an eQTL for , and mRNA expression is reduced in subjects experiencing asthma exacerbations. may be a modulator of RSV latent infection on asthma exacerbations.
呼吸道合胞病毒（RSV）与儿童哮喘有关。然而，并非所有接触 RSV 的儿童都会出现哮喘症状，这可能是因为基因调节了 RSV 对哮喘加重的影响。
本研究旨在确定调节 RSV 潜伏感染对哮喘加重影响的基因。
我们进行了荟萃分析，以调查来自基因表达综合数据库的 RSV 感染差异表达基因（DEGs）。应用表达数量性状基因座（eQTL）方法选择与 DEGs 相关的单核苷酸多态性（SNP）。基于基因的分析用于鉴定与台湾儿童哮喘研究联盟（TCCAS）哮喘加重显著相关的 SNPs，并在独立队列儿童哮喘管理计划（CAMP）中进行验证。进行基因-RSV 相互作用分析，以研究 SNP 和 RSV 潜伏感染对哮喘加重的相互作用之间的关联。
通过对 RSV 相关基因的荟萃分析，共发现 352 个显著的 DEGs。我们使用与 DEGs 相关的 38123 个 SNPs 来研究基因对哮喘加重的遗传主要影响。我们发现，在 TCCAS 中，八个与 RSV 相关的基因（和）与哮喘加重显著相关，并且在 CAMP 中也得到了验证。在 TCCAS 中，rs7251960（）显著调节了 RSV 潜伏感染对哮喘加重的影响（错误发现率<0.05）。rs7251960 变异与肺组织中 mRNA 表达相关（趋势检验 p 值=1.2×10）。在两个独立的数据集的哮喘加重患者的鼻黏膜中，mRNA 的表达降低。
rs7251960 是 的 eQTL，mRNA 的表达在经历哮喘加重的患者中降低。可能是 RSV 潜伏感染对哮喘加重影响的调节剂。
