ArticleAmerican journal of physiology. Lung cellular and molecular physiology2013
Functional promoter variants in sphingosine 1-phosphate receptor 3 associate with susceptibility to sepsis-associated acute respiratory distress syndrome.
Article in American journal of physiology. Lung cellular and molecular physiology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 56 citations in OpenAlex.
- Effects of sphingolipid metabolism related genes-SPTLC1, ORMDL3, SPHK1 and S1PR3 polymorphisms on susceptibility to hashimoto's thyroiditis.Journal of endocrinological investigation · 2025Article
- Integrative multi-omics analysis unravels the host response landscape and reveals a serum protein panel for early prognosis prediction for ARDS.Critical care (London, England) · 2024Observational
- S1PR3 inhibition protects against LPS-induced ARDS by inhibiting NF-κB and improving mitochondrial oxidative phosphorylation.Journal of translational medicine · 2024Article
- A Razor's Edge: Vascular Responses to Acute Inflammatory Lung Injury/Acute Respiratory Distress Syndrome.Annual review of physiology · 2024Review
- MicroRNA-127 promotes anti-microbial ability in porcine alveolar macrophages via S1PR3/TLR signaling pathway.Journal of veterinary science · 2023Article
- Circulating eNAMPT as a biomarker in the critically ill: acute pancreatitis, sepsis, trauma, and acute respiratory distress syndrome.BMC anesthesiology · 2022Article
- A cortactin CTTN coding SNP contributes to lung vascular permeability and inflammatory disease severity in African descent subjects.Translational research : the journal of laboratory and clinical medicine · 2022Article
- 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
- Monitoring and Modulating Inflammation-Associated Alterations in Synaptic Plasticity: Role of Brain Stimulation and the Blood-Brain Interface.Biomolecules · 2021Review
- Identification of an Alveolar Macrophage-Related Core Gene Set in Acute Respiratory Distress Syndrome.Journal of inflammation research · 2021Article
- The acute respiratory distress syndrome biomarker pipeline: crippling gaps between discovery and clinical utility.Translational research : the journal of laboratory and clinical medicine · 2020Review
- Advancements in understanding the role of lysophospholipids and their receptors in lung disorders including bronchopulmonary dysplasia.Biochimica et biophysica acta. Molecular and cell biology of lipids · 2020Review
- Iron and Sphingolipids as Common Players of (Mal)Adaptation to Hypoxia in Pulmonary Diseases.International journal of molecular sciences · 2020Review
- Overexpression of Sphingosine Kinase-1 and Sphingosine-1-Phosphate Receptor-3 in SevereBioMed research international · 2020Article
- Development of a biomarker mortality risk model in acute respiratory distress syndrome.Critical care (London, England) · 2019Article
- Genomic and Genetic Approaches to Deciphering Acute Respiratory Distress Syndrome Risk and Mortality.Antioxidants & redox signaling · 2019Review
- Novel mechanisms regulating endothelial barrier function in the pulmonary microcirculation.The Journal of physiology · 2019Review
- Integrating molecular pathogenesis and clinical translation in sepsis-induced acute respiratory distress syndrome.JCI insight · 2019Review
- Article
- Genome-Wide Association Study in African Americans with Acute Respiratory Distress Syndrome Identifies the Selectin P Ligand Gene as a Risk Factor.American journal of respiratory and critical care medicine · 2018Article
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Authors and funding
18 authors at 5 institutions in 2 countries.
Funding
Abstract
The genetic mechanisms underlying the susceptibility to acute respiratory distress syndrome (ARDS) are poorly understood. We previously demonstrated that sphingosine 1-phosphate (S1P) and the S1P receptor S1PR3 are intimately involved in lung inflammatory responses and vascular barrier regulation. Furthermore, plasma S1PR3 protein levels were shown to serve as a biomarker of severity in critically ill ARDS patients. This study explores the contribution of single nucleotide polymorphisms (SNPs) of the S1PR3 gene to sepsis-associated ARDS. S1PR3 SNPs were identified by sequencing the entire gene and tagging SNPs selected for case-control association analysis in African- and ED samples from Chicago, with independent replication in a European case-control study of Spanish individuals. Electrophoretic mobility shift assays, luciferase activity assays, and protein immunoassays were utilized to assess the functionality of associated SNPs. A total of 80 variants, including 29 novel SNPs, were identified. Because of limited sample size, conclusive findings could not be drawn in African-descent ARDS subjects; however, significant associations were found for two promoter SNPs (rs7022797 -1899T/G; rs11137480 -1785G/C), across two ED samples supporting the association of alleles -1899G and -1785C with decreased risk for sepsis-associated ARDS. In addition, these alleles significantly reduced transcription factor binding to the S1PR3 promoter; reduced S1PR3 promoter activity, a response particularly striking after TNF-α challenge; and were associated with lower plasma S1PR3 protein levels in ARDS patients. These highly functional studies support S1PR3 as a novel ARDS candidate gene and a potential target for individualized therapy.
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