杭州浙大迪迅生物基因工程有限公司Release date：2018-11-13
Clinical & Experimental Allergy
[IF:5.158]
Novel genes and insights in complete asthma remission: A genome-wide association study on clinical and complete asthma remissionDOI: 10.1111/cea.13181
Abstract:
Background: Asthma is a chronic respiratory disease without a cure,although there exists spontaneous remission.Genome-wide association (GWA) studies have pinpointed genes associated with asthma development, but did not investigate asthma remission.
Methods: Clinical remission (ClinR) was defined by the absence of asthma treatment and wheezing in the last year and asthma attacks in the last 3 years and complete remission (ComR) similarly but additionally with normal lung function and absence of bronchial hyperres -ponsiveness (BHR). A GWA study on both ClinR and ComR was performed in 790 asthmatics with initial doctor diagnosis of asthma and BHR and long-term follow-up. We assessed replication of the 25 top single nucleotide polymorphisms (SNPs) in 2 independent cohorts (total n = 456), followed by expression quantitative loci (eQTL) analyses of the 4 replicated SNPs in lung tissue and epithelium.
Results: Of the 790 asthmatics, 178 (23%) had ClinR and 55 ComR (7%) after median follow-up of 15.5 (range 3.3-47.8) years. In ClinR, 1 of the 25 SNPs, rs2740102,replicated in a meta-analysis of the replication cohorts, which was an eQTL for POLI in lung tissue. In ComR, 3 SNPs replicated in a meta-analysis of the replication cohorts. The top-hit, rs6581895, almost reached genome-wide significance (P-value 4.68 9 107) and was an eQTL for FRS2 and CCT in lung tissue. Rs1420101 was a cis-eQTL in lung tissue for IL1RL1 and IL18R1 and a trans-eQTL for IL13.
Conclusions: By defining a strict remission phenotype, we identified 3 SNPs to be associated with complete asthma remission, where 2 SNPs have plausible biological relevance in FRS2, CCT, IL1RL1, IL18R1 and IL13.
First Author:
J. M. Vonk
Correspondence:
Department of Epidemiology, University Medical Center Groningen, University of Groningen,Groningen, The Netherlands
Conclusions
We describe the architecture of the evolution of IgE responses to multiple allergen components throughout childhood, which may facilitate development of better diagnostic and prognostic biomarkers for allergic diseases.
All Authors:
J. M. Vonk, M. A. E. Nieuwenhuis, F. N. Dijk, A. Boudier, V. Siroux, E. Bouzigon, N. Probst-Hensch, M. Imboden, D. Keidel, D. Sin, Y. Bosse, K. Hao, M. van den Berge, A. Faiz, G. H. Koppelman, D. S. Postma
2018-10-25 Article
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