ArticleClinical and translational gastroenterology2014
Higher activity of the inducible nitric oxide synthase contributes to very early onset inflammatory bowel disease.
Article in Clinical and translational gastroenterology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.
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Who cites it
50 citing papers in PubMed, 89 citations in OpenAlex.
- Regulation of Inducible Nitric Oxide Synthase (NOS2) Expression in Healthy and Inflamed Bowel: A Narrative Review.International journal of molecular sciences · 2026Review
- Evaluation of the Anti-Inflammatory Activity of Selected Plant Extracts in an In Vitro Model of Inflammation Using LPS-Stimulated Macrophages.Biomedicines · 2026Article
- Estrogen deprivation induces hepatic inflammation, Indoleamine-2,3-dioxygenase 1, tryptophan catabolism, and plasma cholesterol.Scientific reports · 2026Article
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- Association ofInternational journal of molecular sciences · 2025Article
- Ultra-sensitive metaproteomics redefines the dark metaproteome, uncovering host-microbiome interactions and drug targets in intestinal diseases.Nature communications · 2025Article
- Convergent evolution of oxidized sugar metabolism in commensal and pathogenic microbes in the inflamed gut.Nature communications · 2025Article
- Identification and multimodal characterization of a specialized epithelial cell type associated with Crohn's disease.Nature communications · 2024Article
- Effect of knocking out mouseAmerican journal of physiology. Gastrointestinal and liver physiology · 2024Article
- NOS2 Polymorphism in Aspect of Left and Right-Sided Colorectal Cancer.Journal of clinical medicine · 2024Article
- Rauwolfia polysaccharide can inhibit the progress of ulcerative colitis through NOS2-mediated JAK2/STAT3 pathway.PloS one · 2024Article
- MEK inhibitors increase the mortality rate in mice with LPS-induced inflammation through IL-12-NO signaling.Cell death discovery · 2023Article
- A Specialized Epithelial Cell Type Regulating Mucosal Immunity and Driving Human Crohn's Disease.bioRxiv : the preprint server for biology · 2023Article
- The role of SOD2 and NOS2 genes in the molecular aspect of bladder cancer pathophysiology.Scientific reports · 2023Article
- Impact of diet and host genetics on the murine intestinal mycobiome.Nature communications · 2023Article
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- Article
- Variation of genes encoding nitric oxide synthases and antioxidant enzymes as potential risks of multiple sclerosis development: a preliminary study.Scientific reports · 2022Article
- The Complexity of Sesquiterpene Chemistry Dictates Its Pleiotropic Biologic Effects on Inflammation.Molecules (Basel, Switzerland) · 2022Review
- Interferon-γ primes macrophages for pathogen ligand-induced killing via a caspase-8 and mitochondrial cell death pathway.Immunity · 2022Article
Corrections and comments
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Authors and funding
17 authors at 8 institutions in 5 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectivesThe NOS2 gene encodes for the inducible nitric oxide synthase (iNOS), responsible for nitric oxide (NO) production, which contributes to antimicrobial and antipathogenic activities. Higher levels of both iNOS and NO-induced damage have been observed in inflammatory bowel disease (IBD) patients. NOS2 may have a role in a specific subset of IBD patients with severe and/or extensive colitis. Therefore, the aim of this study is to examine the role of NOS2 in such a subset, very early onset IBD (VEO-IBD).
methodsSeventeen tag single nucleotide polymorphisms (SNPs) in the NOS2 gene were successfully genotyped in VEO-IBD patients. Genetic associations were replicated in an independent VEO-IBD cohort. Functional analysis for iNOS activity was performed on the most significantly associated functional variant.
resultsThe NOS2 rs2297518 SNP was found to be associated in VEO-IBD in two independent cohorts. Upon combined analysis, a coding variant (S608L) showed the strongest association with VEO-IBD (Pcombined=1.13 × 10(-6), OR (odds ratio)=3.398 (95% CI (confidence interval) 2.02-5.717)) as well as associations with VEO-Crohn's disease and VEO-ulcerative colitis (UC). This variant also showed an association with UC diagnosed between 11 and 17 years of age but not with adult-onset IBD (>17 years). B-cell lymphoblastoid cell lines genotyped for the risk variant as well as Henle-407 cells transfected with a plasmid construct with the risk variant showed higher NO production. Colonic biopsies of VEO-IBD patients showed higher immunohistochemical staining of nitrotyrosine, indicating more nitrosative stress and tissue damage.
conclusionsThese studies suggest the importance of iNOS in genetic susceptibility to younger IBD presentation due to higher NO production.
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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.