ArticleMolecular diagnosis & therapy2019
NFKBIZ and CW6 in Adalimumab Response Among Psoriasis Patients: Genetic Association and Alternative Transcript Analysis.
Article in Molecular diagnosis & therapy, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 19 citations in OpenAlex.
- The Nuclear NF-κB Regulator IκBζ: Updates on Its Molecular Functions and Pathophysiological Roles.Cells · 2024Review
- Gene Ontology Analysis Highlights Biological Processes Influencing Responsiveness to Biological Therapy in Psoriasis.Pharmaceutics · 2023Article
- Genetic Influence on Treatment Response in Psoriasis: New Insights into Personalized Medicine.International journal of molecular sciences · 2023Review
- Pharmacogenomics on the Treatment Response in Patients with Psoriasis: An Updated Review.International journal of molecular sciences · 2023Review
- Pharmaco-Omics in Psoriasis: Paving the Way towards Personalized Medicine.International journal of molecular sciences · 2023Review
- Long-Term Drug Survival and Effectiveness of Secukinumab in Patients with Moderate to Severe Chronic Plaque Psoriasis: 42-Month Results from the SUPREME 2.0 Study.Clinical, cosmetic and investigational dermatology · 2023Article
- The central inflammatory regulator IκBζ: induction, regulation and physiological functions.Frontiers in immunology · 2023Review
- Potential Differences in the Cardiometabolic Risk Profile of Patients with Psoriatic Disease according to Their HLA-C∗06 Status.BioMed research international · 2022Observational
- Genetic Variants of the NF-κB Pathway: Unraveling the Genetic Architecture of Psoriatic Disease.International journal of molecular sciences · 2021Review
- Upregulation of NFKBIZ affects bladder cancer progression via the PTEN/PI3K/Akt signaling pathway.International journal of molecular medicine · 2021Article
- The negative feedback loop of NF-κB/miR-376b/NFKBIZ in septic acute kidney injury.JCI insight · 2020Article
- The HLA-Cw6 Dilemma: Is It Really an Outcome Predictor in Psoriasis Patients under Biologic Therapy? A Monocentric Retrospective Analysis.Journal of clinical medicine · 2020Article
- HLA-Cw6 Status and Treatment Responses Between Psoriasis Patients.Indian journal of dermatologyArticle
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Authors and funding
6 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundNuclear factor (NF)-κB is an essential mediator of the tumor necrosis factor (TNF) pathway, and has been implicated in psoriasis. NFKBIZ is a nuclear inhibitor of NF-κB with a prominent role in the pathogenesis of psoriasis. The genetic variation at the NFKBIZ gene has been associated with the risk of developing psoriasis, and could also contribute to defining the response to anti-TNF biological drugs.
objectivesThe objectives of this study were to determine the association of a common NFKBIZ insertion/deletion (indel) polymorphism (rs3217713) with the response to adalimumab and determine the differences in the relative expression of a NFKBIZ alternative transcript in patients with a positive versus negative response.
methodsWe genotyped a common NFKBIZ polymorphism in 169 psoriasis patients treated with adalimumab classified as responders (n = 120) and non-responders (n = 49), according to whether they had a 75% reduction in the Psoriasis Area and Severity Index score (PASI75) at week 24. The Cw6 polymorphism was also determined and allele and genotype frequencies were compared between the groups. We also determined the rate of the expression of a NFKBIZ transcript lacking exon 10 relative to the normal transcript in 60 patients (27 non-responders). In addition, because the intron indel could affect RNA splicing, we investigated whether the level of the alternative transcript was related to the intronic genotype.
resultsThe NFKBIZ polymorphism was associated with adalimumab response, with carriers of the deletion allele significantly more frequent among responders (odds ratio = 2.76, 95% confidence interval 1.19-6.43; p = 0.015). The presence of the HLA-CW6 allele was also associated with a positive response in our cohort (p = 0.018). The alternative transcript was amplified in all the samples. We found higher but non-significant values of normal to alternative transcript in responders as well as in NFKBIZ insertion homozygotes.
conclusionOur study supported a significant effect of a common NFKBIZ polymorphism on the response to adalimumab. This result could help to optimize the prescription of this anti-TNF, but requires confirmation in other cohorts.
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