Nocturnal asthma is affected by genetic interactions between RORA and NPSR1.
Adolescent
Asthma
/ genetics
Child
Circadian Rhythm
Cohort Studies
Cross-Sectional Studies
Databases, Genetic
Female
Genetic Predisposition to Disease
Humans
Hypersensitivity
/ genetics
Male
Nuclear Receptor Subfamily 1, Group F, Member 1
/ genetics
Phenotype
Polymorphism, Single Nucleotide
Receptors, G-Protein-Coupled
/ genetics
Risk Factors
childhood asthma
circadian rhythm
genetic epistasis
nighttime asthma
Journal
Pediatric pulmonology
ISSN: 1099-0496
Titre abrégé: Pediatr Pulmonol
Pays: United States
ID NLM: 8510590
Informations de publication
Date de publication:
06 2019
06 2019
Historique:
received:
23
09
2018
revised:
17
12
2018
accepted:
04
02
2019
pubmed:
31
3
2019
medline:
18
3
2020
entrez:
31
3
2019
Statut:
ppublish
Résumé
Neuropeptide 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. Interaction 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). RORA* 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. RORA* 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.
Sections du résumé
BACKGROUND
Neuropeptide 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.
METHODS
Interaction 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).
RESULTS
RORA* 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.
CONCLUSION
RORA* 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.
Substances chimiques
NPSR1 protein, human
0
Nuclear Receptor Subfamily 1, Group F, Member 1
0
RORA protein, human
0
Receptors, G-Protein-Coupled
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
847-857Subventions
Organisme : Medical Research Council
ID : MR/L012693/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : G0601361
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/K002449/1
Pays : United Kingdom
Informations de copyright
© 2019 Wiley Periodicals, Inc.