微小RNA-107及其与屋尘螨致敏的关联：对哮喘的影响
MiR-107 and Its Association With House Dust Mite Sensitisation: Implications for Asthma.
作者信息
Kim Byung-Keun, Yang Min-Suk, Srivastava Upasna, Piparia Shraddha, Sharma Rinku, Tiwari Anshul, Kho Alvin, Wong Richard, Celedón Juan C, Weiss Scott T, McGeachie Michael, Tantisira Kelan
机构信息
Division of Pediatric Respiratory Medicine, Department of Pediatrics, University of California San Diego, La Jolla, California, USA.
Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea.
出版信息
Clin Exp Allergy. 2025 Jan;55(1):67-74. doi: 10.1111/cea.14590. Epub 2024 Nov 3.
INTRODUCTION
MicroRNAs (miRNAs) have been linked to allergic diseases but their effects on sensitisation to allergens in individuals with asthma are unknown. We aimed to identify miRNAs associated with house dust mite (HDM) sensitisation in childhood asthma.
METHODS
Serum samples from 1126 children with asthma who participated in the Genetics of Asthma in Costa Rica Study (GACRS) were profiled for 304 miRNAs. We first divided according to HDM sensitisation and then tested whether miRNAs were differentially expressed (DE) between the two groups. Gene enrichment analysis for target genes of the DE miRNAs was then performed to identify potential causal pathways. Replication analysis was performed in the Childhood Asthma Management Program (CAMP), in which expression data of 258 miRNAs in 491 children were available. A mediation analysis was conducted to discern relationships between miRNA and phenotype differences according to HDM sensitisation in GACRS cohort.
RESULTS
There were 906 (80.5%) and 220 (19.5%) subjects in the GACRS HDM+ and HDM- groups. Compared with HDM- participants, those in the HDM+ group were more likely to be severe in variables including pulmonary function, oral corticosteroid use and blood tests. A total of 17 miRNAs were DE (p < 0.05) between the two groups, with miR-642a-3p, let-7c-5p and miR-107 most significantly associated with HDM sensitisation. In CAMP, there were 39 DE miRNAs, and increased expression of miR-107 in HDM+ children was replicated in this cohort. In both GACRS and CAMP, the cadherin-binding pathway was enriched in an analysis of target genes for DE miRNA. In a mediation analysis, miR-107 showed significant indirect effects on eosinophil count and total IgE that were mediated by HDM sensitisation.
CONCLUSION
In children with asthma, miR-107 is associated with HDM sensitisation. Furthermore, miR-107 was indirectly associated with total IgE and eosinophil count through HDM sensitisation.
引言
微小RNA（miRNA）与过敏性疾病有关，但其对哮喘患者过敏原致敏的影响尚不清楚。我们旨在确定与儿童哮喘中屋尘螨（HDM）致敏相关的miRNA。
方法
对参与哥斯达黎加哮喘遗传学研究（GACRS）的1126名哮喘儿童的血清样本进行304种miRNA分析。我们首先根据HDM致敏情况进行分组，然后测试两组之间miRNA是否差异表达（DE）。随后对DE miRNA的靶基因进行基因富集分析，以确定潜在的因果途径。在儿童哮喘管理计划（CAMP）中进行了重复分析，该计划中有491名儿童的258种miRNA的表达数据。进行了中介分析，以根据GACRS队列中的HDM致敏情况来识别miRNA与表型差异之间的关系。
结果
GACRS HDM+组和HDM-组分别有906名（80.5%）和220名（19.5%）受试者。与HDM-参与者相比，HDM+组的参与者在包括肺功能、口服糖皮质激素使用和血液检查等变量方面更可能病情严重。两组之间共有17种miRNA差异表达（p < 0.05），其中miR-642a-3p、let-7c-5p和miR-107与HDM致敏最显著相关。在CAMP中，有39种差异表达的miRNA，该队列中重复了HDM+儿童中miR-107表达增加的情况。在GACRS和CAMP中，钙黏蛋白结合途径在对DE miRNA的靶基因分析中均有富集。在中介分析中，miR-107对嗜酸性粒细胞计数和总IgE显示出由HDM致敏介导的显著间接影响。
结论
在哮喘儿童中，miR-107与HDM致敏有关。此外，miR-107通过HDM致敏与总IgE和嗜酸性粒细胞计数间接相关。
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