MiR-107 and Its Association With House Dust Mite Sensitisation: Implications for Asthma.

IF 6.3 2区 医学 Q1 ALLERGY Clinical and Experimental Allergy Pub Date : 2024-11-03 DOI:10.1111/cea.14590
Byung-Keun Kim, Min-Suk Yang, Upasna Srivastava, Shraddha Piparia, Rinku Sharma, Anshul Tiwari, Alvin Kho, Richard Wong, Juan C Celedón, Scott T Weiss, Michael McGeachie, Kelan Tantisira
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Abstract

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.

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MiR-107 及其与屋尘螨致敏性的关系:对哮喘的影响
导言:微RNA(miRNA)与过敏性疾病有关,但它们对哮喘患者对过敏原过敏的影响尚不清楚。我们旨在确定与儿童哮喘患者对屋内尘螨(HDM)过敏有关的 miRNA:我们对参加哥斯达黎加哮喘遗传学研究(GACRS)的 1126 名哮喘患儿的血清样本进行了分析,共检测了 304 个 miRNAs。我们首先根据HDM敏化程度进行了划分,然后检测了两组之间的miRNA是否存在差异表达(DE)。然后对DE miRNA的靶基因进行基因富集分析,以确定潜在的因果关系通路。在儿童哮喘管理项目(CAMP)中进行了复制分析,获得了 491 名儿童中 258 个 miRNA 的表达数据。研究人员还进行了一项中介分析,以确定 miRNA 与 GACRS 队列中 HDM 敏感性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-组受试者相比,HDM+组受试者在肺功能、口服皮质类固醇使用情况和血液检测等变量方面更容易出现严重问题。共有 17 个 miRNA 被 DE(p 结论:在哮喘患儿中,miR-1 和 miR-2 的表达较高:在哮喘儿童中,miR-107 与 HDM 致敏相关。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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来源期刊
CiteScore
10.40
自引率
9.80%
发文量
189
审稿时长
3-8 weeks
期刊介绍: Clinical & Experimental Allergy strikes an excellent balance between clinical and scientific articles and carries regular reviews and editorials written by leading authorities in their field. In response to the increasing number of quality submissions, since 1996 the journals size has increased by over 30%. Clinical & Experimental Allergy is essential reading for allergy practitioners and research scientists with an interest in allergic diseases and mechanisms. Truly international in appeal, Clinical & Experimental Allergy publishes clinical and experimental observations in disease in all fields of medicine in which allergic hypersensitivity plays a part.
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