ArticleAmerican journal of respiratory cell and molecular biology2014
Functional characterization of polymorphisms in the peptidase inhibitor 3 (elafin) gene and validation of their contribution to risk of acute respiratory distress syndrome.
Article in American journal of respiratory cell and molecular biology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed.
- Tiprelestat for treatment of hospitalized COVID-19: results of the double-blind randomized placebo-controlled COMCOVID trial.Advances in therapy · 2025Trial
- Transcriptomic Biomarkers Associated With Microbiological Etiology and Disease Severity in Childhood Pneumonia.The Journal of infectious diseases · 2025Article
- Identification of cuproptosis-realated key genes and pathways in Parkinson's disease via bioinformatics analysis.PloS one · 2024Article
- Personalized medicine using omics approaches in acute respiratory distress syndrome to identify biological phenotypes.Respiratory research · 2022Review
- Innate immune imprints in SARS-CoV-2 Omicron variant infection convalescents.Signal transduction and targeted therapy · 2022Article
- DNA methylation exploration for ARDS: a multi-omics and multi-microarray interrelated analysis.Journal of translational medicine · 2019Article
- Relationship between β-defensin-1 gene polymorphism and susceptibility and prognosis of acute respiratory distress syndrome.Medicine · 2019Article
- Influence of lipopolysaccharide on proinflammatory gene expression in human corneal, conjunctival and meibomian gland epithelial cells.The ocular surface · 2018Article
- The Basic Science and Molecular Mechanisms of Lung Injury and Acute Respiratory Distress Syndrome.International anesthesiology clinics · 2018Review
- Bronchoalveolar Lavage Fluid Protein Expression in Acute Respiratory Distress Syndrome Provides Insights into Pathways Activated in Subjects with Different Outcomes.Scientific reports · 2017Article
- Genetic and epigenetic factors in the regulation of the immune response.Current opinion in pediatrics · 2016Review
- Article
- Beyond single-nucleotide polymorphisms: genetics, genomics, and other 'omic approaches to acute respiratory distress syndrome.Clinics in chest medicine · 2014Review
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10 authors.
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Abstract
Elafin (peptidase inhibitor 3 [PI3]) and its biologically active precursor, pre-elafin, are neutrophil serine proteinase inhibitors with an important role in preventing excessive tissue injury during inflammatory events. Recently, we reported an association between single-nucleotide polymorphism (SNP) rs2664581 in the PI3 gene, increased risk of acute respiratory distress syndrome (ARDS) and pre-elafin circulating levels. This study aims to validate the legitimacy of this association by using a cohort of patients who met the criteria for systemic inflammatory response syndrome and were at risk of developing ARDS (n = 840). A comprehensive functional study of SNPs in PI3 gene was also performed. Luciferase assays and electrophoretic mobility shift assays were conducted to determine the functional relevance of promoter region variants. The effect of the coding SNP rs2664581 on the neutrophil elastase inhibitory activity and transglutaminase binding properties of pre-elafin was also investigated. The variant allele of rs2664581 (C) was significantly associated with increased ARDS risk, mainly among subjects with sepsis (odds ratio = 1.44; 95% confidence interval = 1.04-1.99; P = 0.0276, adjusted by age, sex, and Acute Physiology and Chronic Health Evaluation III). Pre-elafin recombinant protein carrying the amino acid change associated with rs2664581 (Thr34Pro, mutant protein [MT]) had greater capacity to undergo transglutaminase-mediated cross-linking to immobilized fibronectin than wild-type protein in vitro (P < 0.003). No differences were observed in the neutrophil elastase inhibitory activities of wild-type versus MT proteins. In addition, the risk allele-promoter construct had significantly lower cytokine-induced transcriptional activity. Electrophoretic mobility shift assay results indicated a differential binding of nuclear proteins to the G and A alleles of SNP -338G > A. Our results confirm the association between SNP rs2664581 and enhanced risk of ARDS, further supporting the role of PI3 in ARDS development. SNPs in the PI3 locus may act synergistically by regulating PI3 gene expression and pre-elafin biological functions.
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