Universität zu Köln

Gaertner, Vincent D., Michel, Sven, Curtin, John A., Pulkkinen, Ville, Acevedo, Nathalie, Soderhall, Cilla, von Berg, Andrea, Bufe, Albrecht, Laub, Otto, Rietschel, Ernst, Heinzmann, Andrea, Simma, Burkhard, Vogelberg, Christian, Pershagen, Goeran, Melen, Erik, Simpson, Angela ORCID: 0000-0003-2733-6666, Custovic, Adnan ORCID: 0000-0001-5218-7071, Kere, Juha ORCID: 0000-0003-1974-0271 and Kabesch, Michael (2019). Nocturnal asthma is affected by genetic interactions between RORA and NPSR1. Pediatr. Pulmonol., 54 (6). S. 847 - 858. HOBOKEN: WILEY. ISSN 1099-0496

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Abstract

BackgroundNeuropeptide S Receptor 1 (NPSR1) and Retinoid Acid Receptor-Related Orphan Receptor Alpha (RORA ) interact biologically, are both known candidate genes for asthma, and are involved in controlling circadian rhythm. Thus, we assessed (1) whether interactions between RORA and NPSR1 specifically affect the nocturnal asthma phenotype and (2) how this may differ from other asthma phenotypes. MethodsInteraction effects between 24 single-nucleotide polymorphisms (SNPs) in RORA and 35 SNPs in NPSR1 on asthma and nocturnal asthma symptoms were determined in 1432 subjects (763 asthmatics [192 with nocturnal asthma symptoms]; 669 controls) from the Multicenter Asthma Genetic in Childhood/International Study of Asthma and Allergies in Childhood studies. The results were validated and extended in children from the Manchester Asthma and Allergy Study (N=723) and the Children Allergy Milieu Stockholm and Epidemiological cohort (N=1646). ResultsRORA*NPSR1 interactions seemed to affect both asthma and nocturnal asthma. In stratified analyses, however, interactions mainly affected nocturnal asthma and less so asthma without nocturnal symptoms or asthma severity. Results were replicated in two independent cohorts and seemed to remain constant over time throughout youth. ConclusionRORA*NPSR1 interactions appear to be involved in mechanisms specific for nocturnal asthma. In contrast to previous studies focusing on the role of beta 2 receptor polymorphisms in nocturnal asthma as a feature of asthma control or severity in general, our data suggest that changes in circadian rhythm control are associated with nighttime asthma symptoms.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Gaertner, Vincent D. UNSPECIFIED UNSPECIFIED UNSPECIFIED Michel, Sven UNSPECIFIED UNSPECIFIED UNSPECIFIED Curtin, John A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Pulkkinen, Ville UNSPECIFIED UNSPECIFIED UNSPECIFIED Acevedo, Nathalie UNSPECIFIED UNSPECIFIED UNSPECIFIED Soderhall, Cilla UNSPECIFIED UNSPECIFIED UNSPECIFIED von Berg, Andrea UNSPECIFIED UNSPECIFIED UNSPECIFIED Bufe, Albrecht UNSPECIFIED UNSPECIFIED UNSPECIFIED Laub, Otto UNSPECIFIED UNSPECIFIED UNSPECIFIED Rietschel, Ernst UNSPECIFIED UNSPECIFIED UNSPECIFIED Heinzmann, Andrea UNSPECIFIED UNSPECIFIED UNSPECIFIED Simma, Burkhard UNSPECIFIED UNSPECIFIED UNSPECIFIED Vogelberg, Christian UNSPECIFIED UNSPECIFIED UNSPECIFIED Pershagen, Goeran UNSPECIFIED UNSPECIFIED UNSPECIFIED Melen, Erik UNSPECIFIED UNSPECIFIED UNSPECIFIED Simpson, Angela UNSPECIFIED orcid.org/0000-0003-2733-6666 UNSPECIFIED Custovic, Adnan UNSPECIFIED orcid.org/0000-0001-5218-7071 UNSPECIFIED Kere, Juha UNSPECIFIED orcid.org/0000-0003-1974-0271 UNSPECIFIED Kabesch, Michael UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-138698
DOI:	10.1002/ppul.24292
Journal or Publication Title:	Pediatr. Pulmonol.
Volume:	54
Number:	6
Page Range:	S. 847 - 858
Date:	2019
Publisher:	WILEY
Place of Publication:	HOBOKEN
ISSN:	1099-0496
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language CIRCADIAN TRANSCRIPTION; ASSOCIATION; POLYMORPHISMS; RECEPTOR; SYMPTOMS; BETA(2)-ADRENOCEPTOR; VARIANTS; CHILDREN; REVEALS; ALPHA Multiple languages Pediatrics; Respiratory System Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/13869