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:
CreatorsEmailORCIDORCID Put Code
Gaertner, Vincent D.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Michel, SvenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Curtin, John A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Pulkkinen, VilleUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Acevedo, NathalieUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Soderhall, CillaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
von Berg, AndreaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bufe, AlbrechtUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Laub, OttoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Rietschel, ErnstUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Heinzmann, AndreaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Simma, BurkhardUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Vogelberg, ChristianUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Pershagen, GoeranUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Melen, ErikUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Simpson, AngelaUNSPECIFIEDorcid.org/0000-0003-2733-6666UNSPECIFIED
Custovic, AdnanUNSPECIFIEDorcid.org/0000-0001-5218-7071UNSPECIFIED
Kere, JuhaUNSPECIFIEDorcid.org/0000-0003-1974-0271UNSPECIFIED
Kabesch, MichaelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
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:
KeywordsLanguage
CIRCADIAN TRANSCRIPTION; ASSOCIATION; POLYMORPHISMS; RECEPTOR; SYMPTOMS; BETA(2)-ADRENOCEPTOR; VARIANTS; CHILDREN; REVEALS; ALPHAMultiple languages
Pediatrics; Respiratory SystemMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/13869

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