Scientists have identified five pivotal genes that may be linked to the outcome of severe coronavirus disease 2019 (COVID-19) in diabetic kidney patients. The study is currently available at bioRxiv* Prepress server.
Hub genes are those genes that exhibit many interactions with other genes and thus play important roles in regulating vital biological processes.
background
Diabetes is a chronic endocrine disease that increases the risk of severe COVID-19 infection. Evidence indicates that excessive inflammation is the main causative factor for immune complications during the clinical course of COVID-19. However, it remains uncertain how diabetes may increase the risk of the disease.
Diabetic kidney disease, also known as diabetic nephropathy, is a chronic complication of the kidneys caused by high blood sugar. About 30-40% of people with diabetes live with this health condition, and about 50% eventually develop end-stage kidney disease that requires dialysis or a kidney transplant.
Recent evidence has highlighted that patients with diabetic kidney disease and COVID-19 develop multiple pathophysiological mechanisms between lung and kidney. Patients with end-stage kidney disease also show a higher risk of death related to COVID-19.
In the current study, the scientists performed transcriptome and network analysis to identify critical genes shared between the pathways affected by COVID-19 and diabetic kidney disease.
study design
The scientists performed a bioinformatic analysis of transcriptome data obtained from diabetic kidney patients to identify predictive hub genes associated with complications of diabetic kidney disease associated with COVID-19.
They characterized genes that were differently expressed in both disease states. Furthermore, they performed a functional enrichment analysis of the differentially expressed genes in the diabetic kidney disease data set.
To identify the hub genes, they performed a protein-protein interaction network and topological analysis. Finally, they identified the co-expression units of the specific hub genes and assessed their tissue-specific regulation.
Important notes
A total of 995 differentially expressed genes were characterized in the diabetic kidney disease data set. Among these genes, 42 of these genes were linked to COVID-19-related pathways and showed a downregulated expression profile.
A specific set of upregulated differentially expressed genes have been linked to complement and coagulation systems, which are known to be associated with the pathophysiological mechanisms of COVID-19. As reported by the scientists, the interaction between biomolecules associated with clotting and supplementation could significantly worsen COVID-19 outcomes in patients with diabetic kidney disease.
Another set of differentially expressed upregulated genes showed strong associations with pro-inflammatory, cell activation, oxidative stress, cell adhesion, and apoptosis pathways. In addition, some upregulated genes were found to be associated with pathogen recognition receptor pathways, which are vital components of the innate immune system to fight off invading pathogens.
Overall, these observations suggest that overactivation of the innate immune system and inflammatory pathways due to aberrant gene expressions may act in a negative synergistic manner to cause worse COVID-19 outcomes in diabetic kidney patients.
hub genes
Protein-protein network analysis identified a specific set of five central genes, including STAT1, IRF7, ISG15, MX1 and OAS1. Besides their association with COVID-19 and the biological and metabolic pathways associated with diabetic kidney disease, hub genes have shown strong links with heart disease, angiogenesis, and metabolic disease.
The results of the interaction analysis revealed that hub genes are co-expressed with other genes involved in cardiovascular disease, immune response to viruses, and genetic regulation at transcriptional and post-transcriptional levels.
Tissue-specific expression profile analysis of the hub genes revealed that ISG15, STAT1 and MX1 have a down-regulated expression profile in immune cells of COVID-19 patients. In addition, MX1 and OAS1 showed a lower expression profile in healthy kidney tissues.
As reported by the scientists, sustained activation of immune cells in CKD with increased expression of ISG15, STAT1 and MX1 can lead to increased production of pro-inflammatory cytokines and subsequently exacerbate COVID-19 outcomes.
Study the importance
The study identifies five pivotal genes that may play important roles in worsening COVID-19 outcomes in diabetic kidney patients. These genes are associated with the immune system and fungal infections.
These genes could serve as potential predictive or therapeutic targets to facilitate the development of new drugs against COVID-19.
*Important note
bioRxiv publishes preliminary scientific reports that are not subject to peer review, and therefore should not be considered conclusive, guide clinical practice/health-related behavior, or be treated as established information.
Originally published at San Jose News Bulletin
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