ArticleThe Journal of allergy and clinical immunology2010
Functional variants of the sphingosine-1-phosphate receptor 1 gene associate with asthma susceptibility.
Article in The Journal of allergy and clinical immunology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
What it found
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Who cites it
31 citing papers in PubMed, 42 citations in OpenAlex.
- Role of S1PR1 in Modulating Airway Epithelial Responses toPathogens (Basel, Switzerland) · 2025Article
- Effects of sphingolipid metabolism related genes-SPTLC1, ORMDL3, SPHK1 and S1PR3 polymorphisms on susceptibility to hashimoto's thyroiditis.Journal of endocrinological investigation · 2025Article
- Genetic and epigenetic regulation of cortactin (CTTN) by inflammatory factors and mechanical stress in human lung endothelial cells.Bioscience reports · 2024Article
- A Razor's Edge: Vascular Responses to Acute Inflammatory Lung Injury/Acute Respiratory Distress Syndrome.Annual review of physiology · 2024Review
- Hyperoxia-induced S1PCell biochemistry and biophysics · 2021Article
- Genetic and epigenetic regulation of the non-muscle myosin light chain kinase isoform by lung inflammatory factors and mechanical stress.Clinical science (London, England : 1979) · 2021Article
- Lysolipids in Vascular Development, Biology, and Disease.Arteriosclerosis, thrombosis, and vascular biology · 2021Review
- Lysophospholipids in Lung Inflammatory Diseases.Advances in experimental medicine and biology · 2021Article
- Type 2 Inflammation in Eosinophilic Esophagitis: From Pathophysiology to Therapeutic Targets.Frontiers in physiology · 2021Review
- The Metabolomics of Childhood Atopic Diseases: A Comprehensive Pathway-Specific Review.Metabolites · 2020Review
- Direct Extracellular NAMPT Involvement in Pulmonary Hypertension and Vascular Remodeling. Transcriptional Regulation by SOX and HIF-2α.American journal of respiratory cell and molecular biology · 2020Article
- Article
- S1PR1-Associated Molecular Signature Predicts Survival in Patients with Sepsis.Shock (Augusta, Ga.) · 2020Article
- Health Disparities in Patients with Pulmonary Arterial Hypertension: A Blueprint for Action. An Official American Thoracic Society Statement.American journal of respiratory and critical care medicine · 2017Review
- Cutting Edge: Targeting Epithelial ORMDL3 Increases, Rather than Reduces, Airway Responsiveness and Is Associated with Increased Sphingosine-1-Phosphate.Journal of immunology (Baltimore, Md. : 1950) · 2017Article
- Oroscomucoid like protein 3 (ORMDL3) transgenic mice have reduced levels of sphingolipids including sphingosine-1-phosphate and ceramide.The Journal of allergy and clinical immunology · 2017Article
- Endothelial cell signaling and ventilator-induced lung injury: molecular mechanisms, genomic analyses, and therapeutic targets.American journal of physiology. Lung cellular and molecular physiology · 2017Review
- Simvastatin-induced sphingosine 1-phosphate receptor 1 expression is KLF2-dependent in human lung endothelial cells.Pulmonary circulation · 2017Article
- Airway reactivity and sphingolipids-implications for childhood asthma.Molecular and cellular pediatrics · 2015Article
- Common variants of NFE2L2 gene predisposes to acute respiratory distress syndrome in patients with severe sepsis.Critical care (London, England) · 2015Article
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 2 countries.
Funding
Abstract
backgroundThe genetic mechanisms underlying asthma remain unclear. Increased permeability of the microvasculature is a feature of asthma, and the sphingosine-1-phosphate receptor (S1PR1) is an essential participant regulating lung vascular integrity and responses to lung inflammation.
objectiveWe explored the contribution of polymorphisms in the S1PR1 gene to asthma susceptibility.
methodsA combination of gene resequencing for single nucleotide polymorphism (SNP) discovery, case-control association, functional evaluation of associated SNPs, and protein immunochemistry studies was used.
resultsImmunohistochemistry studies demonstrated significantly decreased S1PR1 protein expression in pulmonary vessels in lungs of asthmatic patients compared with those of nonasthmatic subjects (P < .05). Direct DNA sequencing of 27 multiethnic samples identified 39 S1PR1 variants (18 novel SNPs). Association studies were performed based on genotyping results from cosmopolitan tagging SNPs in 3 case-control cohorts from Chicago and New York totaling 1,061 subjects (502 cases and 559 control subjects). The promoter SNP rs2038366 (-1557G/T) was found to be associated with asthma (P = .03) in European Americans. In African Americans an association was found for both asthma and severe asthma for intronic SNP rs3753194 (c.-164+170A/G; P = .006 and P = .040, respectively) and for promoter SNP rs59317557 (-532C/G) with severe asthma (P = .028). Consistent with predicted in silico functionality, alleles of the promoter SNPs rs2038366 (-1557G/T) and rs59317557 (-532C/G) influenced the activity of a luciferase S1PR1 reporter vector in transfected endothelial cells exposed to growth factors (epidermal growth factor, platelet-derived growth factor, and vascular endothelial growth factor) known to be increased in asthmatic airways.
conclusionThese data provide strong support for a role for S1PR1 gene variants in asthma susceptibility and severity.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.