Genetic variants in the NF-κB signaling pathway (NFKB1, NFKBIA, NFKBIZ) and risk of critical outcome among COVID-19 patients

Camblor, Daniel G.; Miranda, Daniel; Albaiceta, Guillermo M.; Amado-Rodríguez, Laura; Cuesta‐Llavona, Elías; Vázquez-Coto, Daniel; Oña, Julia Gómez de; García-Lago, Claudia; Gómez, Juan; Coto, Eliécer

doi:10.1016/j.humimm.2022.06.002

Cited by 13 publications

(7 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In the current study, we found no association of CARD8, IL1B, and NFKB1 polymorphisms with the poor outcome of our cohort of COVID-19 patients. This study confirms previous reports describing the same results in relation to rs6509365 CARD8 [20], rs1143634 IL1B [20,21], rs16944 IL1B [24], and rs28362491 NFKB1 [27]. Regarding IL18 and CASP1, to the best of our knowledge, a relationship of their polymorphisms with COVID-19 exacerbation has not been previously reported.…”

Section: Discussionsupporting

confidence: 91%

Inflammasome-Related Genetic Polymorphisms as Severity Biomarkers of COVID-19

Pulito-Cueto,

Sebastián Mora-Gil,

Ferrer-Pargada

et al. 2024

IJMS

View full text Add to dashboard Cite

The most critical forms of coronavirus disease 2019 (COVID-19) are associated with excessive activation of the inflammasome. Despite the COVID-19 impact on public health, we still do not fully understand the mechanisms by which the inflammatory response influences disease prognosis. Accordingly, we aimed to elucidate the role of polymorphisms in the key genes of the formation and signaling of the inflammasome as biomarkers of COVID-19 severity. For this purpose, a large and well-defined cohort of 377 COVID-19 patients with mild (n = 72), moderate (n = 84), severe (n = 100), and critical (n = 121) infections were included. A total of 24 polymorphisms located in inflammasome-related genes (NLRP3, NLRC4, NLRP1, CARD8, CASP1, IL1B, IL18, NFKB1, ATG16L1, and MIF) were genotyped in all of the patients and in the 192 healthy controls (HCs) (who were without COVID-19 at the time of and before the study) by RT-qPCR. Our results showed that patients with mild, moderate, severe, and critical COVID-19 presented similar allelic and genotypic distribution in all the variants studied. No statistically significant differences in the haplotypic distribution of NLRP3, NLRC4, NLRP1, CARD8, CASP1, IL1B, and ATG16L1 were observed between COVID-19 patients, who were stratified by disease severity. Each stratified group of patients presented a similar genetic distribution to the HCs. In conclusion, our results suggest that the inflammasome polymorphisms studied are not associated with the worsening of COVID-19.

show abstract

Section: Discussionsupporting

confidence: 91%

Inflammasome-Related Genetic Polymorphisms as Severity Biomarkers of COVID-19

Pulito-Cueto,

Sebastián Mora-Gil,

Ferrer-Pargada

et al. 2024

IJMS

View full text Add to dashboard Cite

show abstract

“…Lipin1 coordinates liver metabolism, and IκBζ ameliorates fatty liver by downregulating Lipin1 ( 153 ). The NFKBIZ rs3217713 II genotype has been associated with a higher risk of death among COVID-19 patients with severe infection in the ICU ( 154 ). Hidradenitis suppurativa patients have been shown to carry the NFKBIZ homozygotic variant SNP rs3217713 ( 155 ).…”

Section: Diseases Related To Iκbζ In the Context Of Inflammationmentioning

confidence: 99%

The central inflammatory regulator IκBζ: induction, regulation and physiological functions

Feng

Chen

et al. 2023

Front. Immunol.

View full text Add to dashboard Cite

IκBζ (encoded by NFKBIZ) is the most recently identified IkappaB family protein. As an atypical member of the IkappaB protein family, NFKBIZ has been the focus of recent studies because of its role in inflammation. Specifically, it is a key gene in the regulation of a variety of inflammatory factors in the NF-KB pathway, thereby affecting the progression of related diseases. In recent years, investigations into NFKBIZ have led to greater understanding of this gene. In this review, we summarize the induction of NFKBIZ and then elucidate its transcription, translation, molecular mechanism and physiological function. Finally, the roles played by NFKBIZ in psoriasis, cancer, kidney injury, autoimmune diseases and other diseases are described. NFKBIZ functions are universal and bidirectional, and therefore, this gene may exert a great influence on the regulation of inflammation and inflammation-related diseases.

show abstract

“…In addition, there is no shortage of studies con rming that various herbal medicines for acne can inhibit skin hyperkeratinization, in ammation, and oxidative stress through MAPK and NF-κB pathways [21] . The most common NF-κB dimer is encoded by NFKB1 and NFKBIA [22] , which is precisely the core target of this paper, and it can be hypothesized that TCM is similar to retinoic acid drugs in treating acne by the same mechanism with fewer side effects and without the possible adverse effects of retinoic acid drugs. According to our results, the inhibition of NFKB1 and NFKBIA and thus the reduction of the MAPK signaling pathway may play a crucial role in the treatment of acne with the active ingredients of TCM.…”

Section: Discussionmentioning

confidence: 99%

Network Pharmacology Approach for the Mechanism of Traditional Chinese Medicine in Acne

WANG

Nie

·WANG

et al. 2023

Preprint

View full text Add to dashboard Cite

Objective To explore the molecular mechanism of traditional Chinese medicine (TCM) in the treatment of acne based on network pharmacology. Methods The main active components of TCM were screened by Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP）and Encyclopedia of Traditional Chinese Medicine (ETCM) database and the target was predicted by Swiss Target Prediction website. At the same time, the related targets of ance were screened from Gene Card database, Disgent database, and Therapeutic Target Database (TTD)database. The protein-protein interaction network was constructed using String website and Cytoscape 3.9.1 software after mapping the component target and disease target. Molecular docking technology was used to match potential active components with key targets. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were analyzed by Metascape website. Cytoscape3.9.1 software was used to construct the herb-component-target-pathway network. Results 207 active ingredients and 1722 potential targets were screened from TCM, among which 70 core targets and 20 pathways were closely related to the treatment of acne. Molecular docking results showed that the active ingredients and their key targets had good binding activity. Conclusion TCM has biological support in treating acne. Different proteins have synergistic effects, in which SRC, MAPK1, STAT3, RELA, RXRA, EP300, NFKB1, and NFKBIA, etc. play a key role. Biological processes are mainly involved in hormone synthesis, endocrine regulation, angiogenesis, cell signal transduction, inflammation, etc. These targets are mainly concentrated in multiple signaling pathways such as MAPK and Rap1 signal pathways, which play key roles in anti-inflammatory, anti-skin keratosis, regulation of cell adhesion, repair of the skin barrier, and so on.

show abstract

Genetic variants in the NF-κB signaling pathway (NFKB1, NFKBIA, NFKBIZ) and risk of critical outcome among COVID-19 patients

Cited by 13 publications

References 38 publications

Inflammasome-Related Genetic Polymorphisms as Severity Biomarkers of COVID-19

Inflammasome-Related Genetic Polymorphisms as Severity Biomarkers of COVID-19

The central inflammatory regulator IκBζ: induction, regulation and physiological functions

Network Pharmacology Approach for the Mechanism of Traditional Chinese Medicine in Acne

Contact Info

Product

Resources

About