ArticleThe Journal of allergy and clinical immunology2022
Clinical and molecular implications of RGS2 promoter genetic variation in severe asthma.
Article in The Journal of allergy and clinical immunology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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Who cites it
6 citing papers in PubMed, 5 citations in OpenAlex.
- Type 2-low Asthma: Epidemiology, Multiomics, and Emerging Therapies.Current allergy and asthma reports · 2026Review
- Using cell-specific late-phase asthma mRNA biomarkers to repurpose drugs that concurrently reverse disease signatures across multiple immune cell-types.PLoS computational biology · 2026Article
- Review
- The International Variation in Asthma Phenotypes.Allergy, asthma & immunology research · 2024Article
- A common polymorphism in the Intelectin-1 gene influences mucus plugging in severe asthma.Nature communications · 2024Article
- RGS4 controls airway hyperresponsiveness through GAP-independent mechanisms.The Journal of biological chemistry · 2024Article
Corrections and comments
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Authors and funding
13 authors at 6 institutions in 1 country.
Funding
Abstract
backgroundRegulator of G protein signaling (RGS) 2 terminates bronchoconstrictive Gαq signaling; murine RGS2 knockout demonstrate airway hyperresponsiveness. While RGS2 promoter variants rs2746071 and rs2746072 associate with a clinical mild asthma phenotype, their impact on human airway smooth muscle (HASM) contractility and asthma severity outcomes is unknown.
objectiveWe sought to determine whether reductions in RGS2 expression seen with these 2 RGS2 promoter variants augment HASM contractility and associate with an asthma severity phenotype.
methodsWe transfected HASM with a range of RGS2-specific small interfering RNA (siRNA) concentrations and determined RGS2 protein expression by Western blot analysis and intracellular calcium flux induced by histamine (a Gαq-coupled H1 receptor bronchoconstrictive agonist). We conducted regression-based genotype association analyses of RGS2 variants from 611 patients from the National Heart, Lung, and Blood Institute Severe Asthma Research Program 3.
resultsRGS2-specific siRNA caused dose-dependent increases in histamine-stimulated bronchoconstrictive intracellular calcium signaling (2-way ANOVA, P < .0001) with a concomitant decrease in RGS2 protein expression. RGS2-specific siRNA did not affect Gαq-independent ionomycin-induced intracellular calcium signaling (P = .42). The minor allele frequency of rs2746071 and rs2746072 was 0.46 and 0.28 among African American/non-Hispanic Black patients and was 0.28 and 0.27 among non-Hispanic White patients, among whom these single nucleotide polymorphisms were in stronger linkage disequilibrium (r
conclusionRGS2 promoter variation associates with a molecular and clinical phenotype characterized by enhanced bronchoconstrictive stimulation in vitro and higher asthma exacerbations rates in non-Hispanic White patients.
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Registered trials
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