Novel genes and insights in complete asthma remission: A genome-wide association study on clinical and complete asthma remission.

Autor: Vonk JM; University of Groningen, University Medical Center Groningen, Department of Epidemiology, Groningen, The Netherlands.; University of Groningen, University Medical Center Groningen, Groningen Research Institute for Asthma and COPD (GRIAC), Groningen, The Netherlands., Nieuwenhuis MAE; University of Groningen, University Medical Center Groningen, Groningen Research Institute for Asthma and COPD (GRIAC), Groningen, The Netherlands.; University of Groningen, University Medical Center Groningen, Department of Pulmonology, Groningen, The Netherlands., Dijk FN; University of Groningen, University Medical Center Groningen, Groningen Research Institute for Asthma and COPD (GRIAC), Groningen, The Netherlands.; University of Groningen, University Medical Center Groningen, Department of Pediatric Pulmonology and Pediatric Allergology, Groningen, The Netherlands., Boudier A; INSERM, Team of Environmental Epidemiology applied to Reproduction and Respiratory Health, IAB, Grenoble, France., Siroux V; INSERM, Team of Environmental Epidemiology applied to Reproduction and Respiratory Health, IAB, Grenoble, France.; Team of Environmental Epidemiology applied to Reproduction and Respiratory Health, IAB, Univ. Grenoble Alpes, Grenoble, France.; CHU de Grenoble, Team of Environmental Epidemiology applied to Reproduction and Respiratory Health, IAB, Grenoble, France., Bouzigon E; UMR-946, Inserm, Paris, France.; Sorbonne Paris Cité, Institut Universitaire d'Hématologie, Université Paris Diderot, Paris, France., Probst-Hensch N; Swiss Tropical and Public Health Institute, Basel, Switzerland.; University of Basel, Basel, Switzerland., Imboden M; Swiss Tropical and Public Health Institute, Basel, Switzerland.; University of Basel, Basel, Switzerland., Keidel D; Swiss Tropical and Public Health Institute, Basel, Switzerland.; University of Basel, Basel, Switzerland., Sin D; St Paul's Hospital, The University of British Columbia James Hogg Research Laboratory, Vancouver, BC, Canada.; Respiratory Division, Department of Medicine, University of British Columbia, Vancouver, BC, Canada., Bossé Y; Institut Universitaire de Cardiologie et de Pneumologie de Québec, Department of Molecular Medicine, Laval University, Québec, QC, Canada., Hao K; Merck Research Laboratories, Boston, MA, USA., van den Berge M; University of Groningen, University Medical Center Groningen, Groningen Research Institute for Asthma and COPD (GRIAC), Groningen, The Netherlands.; University of Groningen, University Medical Center Groningen, Department of Pulmonology, Groningen, The Netherlands., Faiz A; University of Groningen, University Medical Center Groningen, Groningen Research Institute for Asthma and COPD (GRIAC), Groningen, The Netherlands.; University of Groningen, University Medical Center Groningen, Department of Pulmonology, Groningen, The Netherlands., Koppelman GH; University of Groningen, University Medical Center Groningen, Groningen Research Institute for Asthma and COPD (GRIAC), Groningen, The Netherlands.; University of Groningen, University Medical Center Groningen, Department of Pediatric Pulmonology and Pediatric Allergology, Groningen, The Netherlands., Postma DS; University of Groningen, University Medical Center Groningen, Groningen Research Institute for Asthma and COPD (GRIAC), Groningen, The Netherlands.; University of Groningen, University Medical Center Groningen, Department of Pulmonology, Groningen, The Netherlands.
Jazyk: angličtina
Zdroj: Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology [Clin Exp Allergy] 2018 Oct; Vol. 48 (10), pp. 1286-1296. Date of Electronic Publication: 2018 Jun 19.
DOI: 10.1111/cea.13181
Abstrakt: 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.
Objective: We performed a GWA study to develop insights in 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 hyperresponsiveness (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 × 10 -7 ) 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 and Clinical Relevance: 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.
(© 2018 John Wiley & Sons Ltd.)
Databáze: MEDLINE
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