ArticlePLoS pathogens2012
HMOX1 gene promoter alleles and high HO-1 levels are associated with severe malaria in Gambian children.
Article in PLoS pathogens, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers, 4 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
56 citing papers in PubMed, 4 syntheses or guidelines pooled it, 96 citations in OpenAlex.
- Intratumoral pro-oxidants promote cancer immunotherapy by recruiting and reprogramming neutrophils to eliminate tumors.Cancer immunology, immunotherapy : CII · 2023Pooled it
- HMOX1 STR polymorphism and malaria: an analysis of a large clinical dataset.Malaria journal · 2022Pooled it
- Pooled it
- The Role of Heme Oxygenase-1 Promoter Polymorphisms in Perinatal Disease.International journal of environmental research and public health · 2021Pooled it
- Trial
- Plasma advanced oxidative protein products are associated with anti-oxidative stress pathway genes and malaria in a longitudinal cohort.Malaria journal · 2014Trial
- Plasmodium falciparum subverts neutrophil function via host miR-451a loaded extracellular vesicles driving bacterial and fungal superinfection susceptibility.PLoS pathogens · 2026Article
- Heme oxygenase-1 emerges as a critical regulator linking autophagy dysregulation, immune infiltration, and NOD-Like receptor signaling in PCOS pathogenesis.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026Article
- Plasma haem oxygenase-1 and interleukin-6 as adjunct host biomarkers associated with malaria.Frontiers in immunology · 2026Article
- Heme oxygenase-1 and malaria pathogenesis.Frontiers in immunology · 2026Review
- Human genetic variations conferring resistance to malaria.Journal of translational medicine · 2025Review
- Utility of Carboxyhemoglobin Level for the Diagnosis of Invasive Bacterial Infection in a Febrile Neonate at Paediatric Emergency Department.Sultan Qaboos University medical journal · 2025Article
- Phenotypic Associations With the HMOX1 GT(n) Repeat in European Populations.American journal of epidemiology · 2024Article
- Targeting circulating labile heme as a defense strategy against malaria.Life science alliance · 2024Article
- Impact of Oxidative Stress on Risk of Death and Readmission in African Children With Severe Malaria: A Prospective Observational Study.The Journal of infectious diseases · 2022Observational
- Article
- Immune Modulation by Inhibitors of the HO System.International journal of molecular sciences · 2020Review
- Modulation of Inflammation and Immune Responses by Heme Oxygenase-1: Implications for Infection with Intracellular Pathogens.Antioxidants (Basel, Switzerland) · 2020Review
- The role of host defences in Covid 19 and treatments thereof.Molecular medicine (Cambridge, Mass.) · 2020Review
- Heme oxygenase-1 in protozoan infections: A tale of resistance and disease tolerance.PLoS pathogens · 2020Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
17 authors at 7 institutions in 5 countries.
Funding
Abstract
Heme oxygenase 1 (HO-1) is an essential enzyme induced by heme and multiple stimuli associated with critical illness. In humans, polymorphisms in the HMOX1 gene promoter may influence the magnitude of HO-1 expression. In many diseases including murine malaria, HO-1 induction produces protective anti-inflammatory effects, but observations from patients suggest these may be limited to a narrow range of HO-1 induction, prompting us to investigate the role of HO-1 in malaria infection. In 307 Gambian children with either severe or uncomplicated P. falciparum malaria, we characterized the associations of HMOX1 promoter polymorphisms, HMOX1 mRNA inducibility, HO-1 protein levels in leucocytes (flow cytometry), and plasma (ELISA) with disease severity. The (GT)(n) repeat polymorphism in the HMOX1 promoter was associated with HMOX1 mRNA expression in white blood cells in vitro, and with severe disease and death, while high HO-1 levels were associated with severe disease. Neutrophils were the main HO-1-expressing cells in peripheral blood, and HMOX1 mRNA expression was upregulated by heme-moieties of lysed erythrocytes. We provide mechanistic evidence that induction of HMOX1 expression in neutrophils potentiates the respiratory burst, and propose this may be part of the causal pathway explaining the association between short (GT)(n) repeats and increased disease severity in malaria and other critical illnesses. Our findings suggest a genetic predisposition to higher levels of HO-1 is associated with severe illness, and enhances the neutrophil burst leading to oxidative damage of endothelial cells. These add important information to the discussion about possible therapeutic manipulation of HO-1 in critically ill patients.
Indexed as
Identifiers
What OpenQuestion holds
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.