Trial reportAmerican journal of respiratory and critical care medicine2014
A functional synonymous coding variant in the IL1RN gene is associated with survival in septic shock.
Trial report in American journal of respiratory and critical care medicine, 2014. 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, 47 citations in OpenAlex.
- Mortality Benefit of Recombinant Human Interleukin-1 Receptor Antagonist for Sepsis Varies by Initial Interleukin-1 Receptor Antagonist Plasma Concentration.Critical care medicine · 2018Trial
- Human genetic and metabolite variation reveals that methylthioadenosine is a prognostic biomarker and an inflammatory regulator in sepsis.Science advances · 2017Trial
- Estrogen receptor β deficiency increases susceptibility to sepsis through metabolic reprogramming-induced macrophage pyroptosis.The Journal of clinical investigation · 2026Article
- Loss of IL1RA promotes prostate cancer growth and metastasis by activating Akt signaling pathway.PloS one · 2026Article
- Genetic associations in sepsis and ARDS.Frontiers in pharmacology · 2026Review
- Obeticholic acid ameliorates sepsis-induced renal mitochondrial damage by inhibiting the NF-κb signaling pathway.Renal failure · 2024Article
- [Mechanism of Extracellular Histone-Induced Endothelial Dysfunction Leading to Sepsis-Induced Acute Respiratory Distress Syndrome].Sichuan da xue xue bao. Yi xue ban = Journal of Sichuan University. Medical science edition · 2024Article
- NLRP6 negatively regulates host defense against polymicrobial sepsis.Frontiers in immunology · 2024Article
- Genetic polymorphisms, biomarkers and signaling pathways associated with septic shock: from diagnosis to therapeutic targets.Burns & trauma · 2024Review
- Association of cytokine gene polymorphisms with peripheral neuropathy susceptibility in people living with HIV in Greece.Journal of neurovirology · 2023Article
- Age and Cytokine Gene Variants Modulate the Immunogenicity and Protective Effect of SARS-CoV-2 mRNA-Based Vaccination.Vaccines · 2023Article
- Acute respiratory distress syndrome heterogeneity and the septic ARDS subgroup.Frontiers in immunology · 2023Review
- Biomarkers for the Prediction and Judgement of Sepsis and Sepsis Complications: A Step towardsJournal of clinical medicine · 2022Review
- New Insights into Clinical and Mechanistic Heterogeneity of the Acute Respiratory Distress Syndrome: Summary of the Aspen Lung Conference 2021.American journal of respiratory cell and molecular biology · 2022Article
- Individual genetic variability mainly of Proinflammatory cytokines, cytokine receptors, and toll-like receptors dictates pathophysiology of COVID-19 disease.Journal of medical virology · 2022Review
- Homeostatic regulation of T follicular helper and antibody response to particle antigens by IL-1Ra of medullary sinus macrophage origin.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- The impact of certain genetic variants (single nucleotide polymorphisms) on incidence and severity of COVID-19.The journal of gene medicine · 2021Article
- Article
- Autophagy Regulation on Pyroptosis: Mechanism and Medical Implication in Sepsis.Mediators of inflammation · 2021Review
- IL-1β suppression of VE-cadherin transcription underlies sepsis-induced inflammatory lung injury.The Journal of clinical investigation · 2020Article
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Authors and funding
14 authors at 4 institutions in 3 countries.
Funding
Abstract
rationaleDeath from infection is a highly heritable trait, yet there are few genetic variants with known mechanism influencing survival during septic shock.
objectivesWe hypothesized that a synonymous coding variant in the IL-1 receptor antagonist gene (IL1RN), rs315952, previously associated with reduced risk for acute respiratory distress syndrome, would be functional and associate with improved survival in septic shock.
methodsWe used a human endotoxin (LPS) model of evoked inflammatory stress to measure plasma IL-1 receptor antagonist (IL1RA) following low-dose Food and Drug Administration-grade LPS injection (1 ng/kg) in 294 human volunteers. RNA sequencing of adipose tissue pre- and post-LPS was used to test for allelic imbalance at rs315952. In the Vasopressin and Septic Shock Trial cohort, we performed a genetic association study for survival, mortality, and organ failure-free days. MEASUREMENTS AND MAIN
resultsAdipose tissue displayed significant allelic imbalance favoring the rs315952C allele in subjects of European ancestry. Consistent with this, carriers of rs315952C had slightly higher plasma IL1RA at baseline (0.039) and higher evoked IL1RA post-LPS (0.011). In the Vasopressin and Septic Shock Trial cohort, rs315952C associated with improved survival (P = 0.028), decreased adjusted 90-day mortality (P = 0.044), and faster resolution of shock (P = 0.029).
conclusionsIn European ancestry subjects, the IL1RN variant rs315952C is preferentially transcribed and associated with increased evoked plasma IL1RA and with improved survival from septic shock. It may be that genetically determined IL1RA levels influence survival from septic shock.
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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.