ArticlePloS one2014
Autophagy-related IRGM polymorphism is associated with mortality of patients with severe sepsis.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers, 1 of them a synthesis that pooled it.
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Who cites it
41 citing papers in PubMed, 1 synthesis or guideline pooled it, 62 citations in OpenAlex.
- The relationship between toll like receptor 4 gene rs4986790 and rs4986791 polymorphisms and sepsis susceptibility: A meta-analysis.Scientific reports · 2016Pooled it
- Differential roles for Irgm1 in myeloid cells for immune resistance to pathogenic bacteria.Journal of leukocyte biology · 2025Article
- Autophagy and Bacterial infections.Autophagy reports · 2025Review
- Type I interferon signaling and peroxisomal dysfunction contribute to enhanced inflammatory cytokine production in IRGM1-deficient macrophages.The Journal of biological chemistry · 2024Article
- Neuron-specific deficiency of autophagy increases neuronal loss in traumatic brain injury.PNAS nexus · 2024Article
- Article
- Restriction and evasion: a review of IFNγ-mediated cell-autonomous defense pathways during genital Chlamydia infection.Pathogens and disease · 2024Review
- Race-specific association of an IRGM risk allele with cytokine expression in human subjects.Scientific reports · 2023Article
- Myeloid autophagy genes protect mice against fatal TNF- and LPS-induced cytokine storm syndromes.Autophagy · 2023Article
- Selective autophagy of RIPosomes maintains innate immune homeostasis during bacterial infection.The EMBO journal · 2022Article
- Autophagopathies: from autophagy gene polymorphisms to precision medicine for human diseases.Autophagy · 2022Article
- How did we get here? Insights into mechanisms of immunity-related GTPase targeting to intracellular pathogens.Current opinion in microbiology · 2022Review
- Immunity-related GTPase IRGM at the intersection of autophagy, inflammation, and tumorigenesis.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2022Review
- Irgm1 regulates metabolism and function in T cell subsets.Scientific reports · 2022Article
- Interactions of Autophagy and the Immune System in Health and Diseases.Autophagy reports · 2022Article
- Role of Intestinal Alkaline Phosphatase in Innate Immunity.Biomolecules · 2021Review
- CXCR5 down-regulation alleviates cognitive dysfunction in a mouse model of sepsis-associated encephalopathy: potential role of microglial autophagy and the p38MAPK/NF-κB/STAT3 signaling pathway.Journal of neuroinflammation · 2021Article
- A Thrombomodulin Promoter Gene Polymorphism, rs2239562, Influences Both Susceptibility to and Outcome of Sepsis.Frontiers in medicine · 2021Article
- Shedding Light on Autophagy During Human Tuberculosis. A Long Way to Go.Frontiers in cellular and infection microbiology · 2021Review
- Dynamin-related Irgm proteins modulate LPS-induced caspase-11 activation and septic shock.EMBO reports · 2020Article
Corrections and comments
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Authors and funding
12 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectiveAutophagy is the regulated catabolic process for recycling damaged or unnecessary organelles, which plays crucial roles in cell survival during nutrient deficiency, and innate immune defense against pathogenic microorganisms. Autophagy has been also reported to be involved in various conditions including inflammatory diseases. IRGM (human immunity-related GTPase) has an important function in eliminating Mycobacterium tuberculosis from host cells via autophagy. We examined the association between genetic polymorphism and clinical course/outcome in severely septic patients.
methodsThe study included 125 patients with severe sepsis/septic shock (SS) and 104 non-sepsis patients who were admitted to the intensive care unit (ICU) of Chiba University Hospital between October 2001 and September 2008 (discovery cohort) and 268 SS patients and 454 non-sepsis patients who were admitted to ICUs of five Japanese institutions including Chiba University Hospital between October 2008 and September 2012 (multi-center validation cohort). Three hundred forty seven healthy volunteers who consented to this study were also included. Genotyping was performed for a single-nucleotide polymorphism (SNP) within the coding region of IRGM, IRGM(+313) (rs10065172). Lipopolysaccharide challenge of whole blood from randomly selected healthy volunteers (n = 70) was performed for comparison of IRGM mRNA expression among different genotypes.
resultsNo significant difference in genotypic distributions (CC/CT/TT) at the IRGM(+313) locus was observed among the three subject groups (SS, non-sepsis, and healthy volunteers) in either cohort. When mortality were compared, no significant difference was observed in the non-sepsis group, while TT homozygotes exhibited a significantly higher mortality than the CC+CT genotype category in the SS group for both cohorts (P = 0.043, 0.037). Lipopolysaccharide challenge to whole blood showed a significant suppression of IRGM mRNA expression in TT compared with the CC+CT genotype category (P = 0.019).
conclusionsThe data suggest that the IRGM(+313), an autophagy-related polymorphic locus, influences outcome in severely septic patients, with the possible involvement of autophagy in sepsis exacerbation.
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