ArticleEMBO molecular medicine2024
Rare coding variants in NOX4 link high ROS levels to psoriatic arthritis mutilans.
Article in EMBO molecular medicine, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
What it found
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Who cites it
6 citing papers in PubMed, 8 citations in OpenAlex.
- Reactive oxygen species in skin diseases: pathogenic mechanisms and nanomaterial-based therapeutic strategies.Frontiers in bioengineering and biotechnology · 2026Review
- The Genetic Puzzle of the Stress-Induced Cardiomyopathy (Takotsubo Syndrome): State of Art and Future Perspectives.Biomolecules · 2025Review
- Emerging Contaminants: An Important But Ignored Risk Factor for Psoriasis.Clinical reviews in allergy & immunology · 2025Review
- Identification of crosstalk genes and diagnostic biomarkers in systemic sclerosis associated sarcopenia through integrative analysis and machine learning.Frontiers in immunology · 2025Article
- NOX2 mediates NLRP3/ROS facilitating nasal mucosal epithelial inflammation in chronic rhinosinusitis with nasal polyps.Heliyon · 2024Article
- [Advances in the Application of Nanozymes in Joint Disease Therapy].Sichuan da xue xue bao. Yi xue ban = Journal of Sichuan University. Medical science edition · 2024Review
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Authors and funding
15 authors at 7 institutions in 4 countries.
Funding
Abstract
Psoriatic arthritis mutilans (PAM) is the rarest and most severe form of psoriatic arthritis, characterized by erosions of the small joints and osteolysis leading to joint disruption. Despite its severity, the underlying mechanisms are unknown, and no susceptibility genes have hitherto been identified. We aimed to investigate the genetic basis of PAM by performing massive parallel sequencing in sixty-one patients from the PAM Nordic cohort. We found rare variants in the NADPH oxidase 4 (NOX4) in four patients. In silico predictions show that the identified variants are potentially damaging. NOXs are the only enzymes producing reactive oxygen species (ROS). NOX4 is specifically involved in the differentiation of osteoclasts, the cells implicated in bone resorption. Functional follow-up studies using cell culture, zebrafish models, and measurement of ROS in patients uncovered that these NOX4 variants increase ROS levels both in vitro and in vivo. We propose NOX4 as the first candidate susceptibility gene for PAM. Our study links high levels of ROS caused by NOX4 variants to the development of PAM, offering a potential therapeutic target.
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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.