ArticlePloS one2013
Interaction between retinoid acid receptor-related orphan receptor alpha (RORA) and neuropeptide S receptor 1 (NPSR1) in asthma.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 33 citations in OpenAlex.
- Retinoic-Acid-Related Orphan Receptor Alpha Is Involved in the Regulation of the Cytoskeleton of Hair Follicle Stem Cells.Biomolecules · 2025Article
- Retinoic Acid-Related Orphan Receptor α Is Required for Generation of Th2 Cells in Type 2 Pulmonary Inflammation.Journal of immunology (Baltimore, Md. : 1950) · 2023Article
- Translational Analysis of Moderate to Severe Asthma GWAS Signals Into Candidate Causal Genes and Their Functional, Tissue-Dependent and Disease-Related Associations.Frontiers in allergy · 2021Article
- Circulating exosomal microRNA-18a-5p accentuates intestinal inflammation in Hirschsprung-associated enterocolitis by targeting RORA.American journal of translational research · 2021Article
- Why Lungs Keep Time: Circadian Rhythms and Lung Immunity.Annual review of physiology · 2020Review
- Nuclear Receptors in Asthma: Empowering Classical Molecules Against a Contemporary Ailment.Frontiers in immunology · 2020Review
- Genomics of asthma, allergy and chronic rhinosinusitis: novel concepts and relevance in airway mucosa.Clinical and translational allergy · 2020Review
- Immune-related gene polymorphisms in pulmonary diseases.Toxicology · 2017Review
- Neuropeptide S (NPS) variants modify the signaling and risk effects of NPS Receptor 1 (NPSR1) variants in asthma.PloS one · 2017Article
- Article
- Genetic Correlates of Individual Differences in Sleep Behavior of Free-Living Great Tits (Parus major).G3 (Bethesda, Md.) · 2016Article
- Cysteinyl Leukotrienes Pathway Genes, Atopic Asthma and Drug Response: From Population Isolates to Large Genome-Wide Association Studies.Frontiers in pharmacology · 2016Review
- GIMAP GTPase family genes: potential modifiers in autoimmune diabetes, asthma, and allergy.Journal of immunology (Baltimore, Md. : 1950) · 2015Article
- Clock gene variants differentiate mood disorders.Molecular biology reports · 2015Article
- Epistasis between serine protease inhibitor Kazal-type 5 (SPINK5) and thymic stromal lymphopoietin (TSLP) genes contributes to childhood asthma.The Journal of allergy and clinical immunology · 2014Article
- Neuropeptide S receptor 1 (NPSR1) activates cancer-related pathways and is widely expressed in neuroendocrine tumors.Virchows Archiv : an international journal of pathology · 2014Article
- Epistatic effects of multiple receptor genes on pathophysiology of asthma - its limits and potential for clinical application.Medical science monitor : international medical journal of experimental and clinical research · 2014Review
- Rule-based models of the interplay between genetic and environmental factors in childhood allergy.PloS one · 2013Article
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Authors and funding
22 authors at 7 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Retinoid acid receptor-related Orphan Receptor Alpha (RORA) was recently identified as a susceptibility gene for asthma in a genome-wide association study. To investigate the impact of RORA on asthma susceptibility, we performed a genetic association study between RORA single nucleotide polymorphisms (SNPs) in the vicinity of the asthma-associated SNP (rs11071559) and asthma-related traits. Because the regulatory region of a previously implicated asthma susceptibility gene, Neuropeptide S receptor 1 (NPSR1), has predicted elements for RORA binding, we hypothesized that RORA may interact biologically and genetically with NPSR1. 37 RORA SNPs and eight NPSR1 SNPs were genotyped in the Swedish birth cohort BAMSE (2033 children) and the European cross-sectional PARSIFAL study (1120 children). Seven RORA SNPs confined into a 49 kb region were significantly associated with physician-diagnosed childhood asthma. The most significant association with rs7164773 (T/C) was driven by the CC genotype in asthma cases (OR = 2.0, 95%CI 1.36-2.93, p = 0.0003 in BAMSE; and 1.61, 1.18-2.19, p = 0.002 in the combined BAMSE-PARSIFAL datasets, respectively), and strikingly, the risk effect was dependent on the Gln344Arg mutation in NPSR1. In cell models, stimulation of NPSR1 activated a pathway including RORA and other circadian clock genes. Over-expression of RORA decreased NPSR1 promoter activity further suggesting a regulatory loop between these genes. In addition, Rora mRNA expression was lower in the lung tissue of Npsr1 deficient mice compared to wildtype littermates during the early hours of the light period. We conclude that RORA SNPs are associated with childhood asthma and show epistasis with NPSR1, and the interaction between RORA and NPSR1 may be of biological relevance. Combinations of common susceptibility alleles and less common functional polymorphisms may modify the joint risk effects on asthma susceptibility.
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