Gene Polymorphisms of Epithelial Cell-Derived Alarmins and Their Effects on Protein Levels and Disease Severity in Patients with COVID-19
Background: The immune response in COVID-19 is characterized by the release of alarmin cytokines, which play crucial roles in immune activation and inflammation. The interplay between these cytokines and genetic variations may influence disease severity and outcomes, while sex differences might furt...
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| Format: | Article |
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MDPI AG
2023-08-01
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| Series: | Genes |
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| Online Access: | https://www.mdpi.com/2073-4425/14/9/1721 |
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| author | Maral Ranjbar Ruth P. Cusack Christiane E. Whetstone Shiraz Nawaz Christopher Khoury Jennifer Wattie Lesley Wiltshire Jennifer Le Roux Eric Cheng Thivya Srinathan Terence Ho Roma Sehmi MyLinh Duong Gail M. Gauvreau |
| author_facet | Maral Ranjbar Ruth P. Cusack Christiane E. Whetstone Shiraz Nawaz Christopher Khoury Jennifer Wattie Lesley Wiltshire Jennifer Le Roux Eric Cheng Thivya Srinathan Terence Ho Roma Sehmi MyLinh Duong Gail M. Gauvreau |
| author_sort | Maral Ranjbar |
| collection | DOAJ |
| description | Background: The immune response in COVID-19 is characterized by the release of alarmin cytokines, which play crucial roles in immune activation and inflammation. The interplay between these cytokines and genetic variations may influence disease severity and outcomes, while sex differences might further contribute to variations in the immune response. Methods: We measured the levels of alarmin cytokines in a cohort of COVID-19 and non-COVID-19 patients using a sensitive Meso Scale Discovery system. Additionally, we conducted an SNP analysis to identify genetic variations within the <i>IL-33</i> and <i>TSLP</i> genes. The association between these genetic variations, cytokine production, and COVID-19 severity was examined. Results: Our findings revealed elevated levels of IL-33 and IL-25 in COVID-19-positive patients compared to COVID-19-negative patients (<i>p</i> < 0.05), indicating their potential as therapeutic targets for disease modulation. Moreover, a minor allele within the IL-33 gene (rs3939286) was found to be associated with a protective effect against severe COVID-19 (<i>p</i> < 0.05), and minor alleles of the <i>TSLP</i> gene (rs2289276 and rs13806933) were found to significantly reduce TSLP protein levels in serum (<i>p</i> < 0.05). Sex-specific effects of <i>TSLP</i> and <i>IL-33</i> SNPs were observed, suggesting a potential influence of sex hormones and genetic variations on the regulation of cytokine production. Conclusion: The present study highlights the importance of alarmin cytokines and genetic variations in COVID-19 severity, providing valuable insights into personalized treatment approaches. Our results suggest that targeting alarmin cytokines may offer potential therapeutic benefits in managing COVID-19. Furthermore, the sex-specific effects of genetic variations emphasize the need to consider individual genetic profiles and sex differences when designing targeted interventions. |
| first_indexed | 2024-03-10T22:43:48Z |
| format | Article |
| id | doaj.art-df02af94c1024b688cf18073010edaf9 |
| institution | Directory Open Access Journal |
| issn | 2073-4425 |
| language | English |
| last_indexed | 2024-03-10T22:43:48Z |
| publishDate | 2023-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Genes |
| spelling | doaj.art-df02af94c1024b688cf18073010edaf92023-11-19T10:52:47ZengMDPI AGGenes2073-44252023-08-01149172110.3390/genes14091721Gene Polymorphisms of Epithelial Cell-Derived Alarmins and Their Effects on Protein Levels and Disease Severity in Patients with COVID-19Maral Ranjbar0Ruth P. Cusack1Christiane E. Whetstone2Shiraz Nawaz3Christopher Khoury4Jennifer Wattie5Lesley Wiltshire6Jennifer Le Roux7Eric Cheng8Thivya Srinathan9Terence Ho10Roma Sehmi11MyLinh Duong12Gail M. Gauvreau13Department of Medicine, Division of Respirology, McMaster University, Hamilton, ON L8N 3Z5, CanadaDepartment of Medicine, Division of Respirology, McMaster University, Hamilton, ON L8N 3Z5, CanadaDepartment of Medicine, Division of Respirology, McMaster University, Hamilton, ON L8N 3Z5, CanadaDepartment of Medicine, Division of Respirology, McMaster University, Hamilton, ON L8N 3Z5, CanadaDepartment of Medicine, Division of Respirology, McMaster University, Hamilton, ON L8N 3Z5, CanadaDepartment of Medicine, Division of Respirology, McMaster University, Hamilton, ON L8N 3Z5, CanadaDepartment of Medicine, Division of Respirology, McMaster University, Hamilton, ON L8N 3Z5, CanadaHamilton Health Sciences, Hamilton, ON L8N 3Z5, CanadaSt. Joseph’s Healthcare Hamilton, Hamilton, ON L8N 4A6, CanadaSt. Joseph’s Healthcare Hamilton, Hamilton, ON L8N 4A6, CanadaDepartment of Medicine, Division of Respirology, McMaster University, Hamilton, ON L8N 3Z5, CanadaDepartment of Medicine, Division of Respirology, McMaster University, Hamilton, ON L8N 3Z5, CanadaDepartment of Medicine, Division of Respirology, McMaster University, Hamilton, ON L8N 3Z5, CanadaDepartment of Medicine, Division of Respirology, McMaster University, Hamilton, ON L8N 3Z5, CanadaBackground: The immune response in COVID-19 is characterized by the release of alarmin cytokines, which play crucial roles in immune activation and inflammation. The interplay between these cytokines and genetic variations may influence disease severity and outcomes, while sex differences might further contribute to variations in the immune response. Methods: We measured the levels of alarmin cytokines in a cohort of COVID-19 and non-COVID-19 patients using a sensitive Meso Scale Discovery system. Additionally, we conducted an SNP analysis to identify genetic variations within the <i>IL-33</i> and <i>TSLP</i> genes. The association between these genetic variations, cytokine production, and COVID-19 severity was examined. Results: Our findings revealed elevated levels of IL-33 and IL-25 in COVID-19-positive patients compared to COVID-19-negative patients (<i>p</i> < 0.05), indicating their potential as therapeutic targets for disease modulation. Moreover, a minor allele within the IL-33 gene (rs3939286) was found to be associated with a protective effect against severe COVID-19 (<i>p</i> < 0.05), and minor alleles of the <i>TSLP</i> gene (rs2289276 and rs13806933) were found to significantly reduce TSLP protein levels in serum (<i>p</i> < 0.05). Sex-specific effects of <i>TSLP</i> and <i>IL-33</i> SNPs were observed, suggesting a potential influence of sex hormones and genetic variations on the regulation of cytokine production. Conclusion: The present study highlights the importance of alarmin cytokines and genetic variations in COVID-19 severity, providing valuable insights into personalized treatment approaches. Our results suggest that targeting alarmin cytokines may offer potential therapeutic benefits in managing COVID-19. Furthermore, the sex-specific effects of genetic variations emphasize the need to consider individual genetic profiles and sex differences when designing targeted interventions.https://www.mdpi.com/2073-4425/14/9/1721COVID-19severityalarminssingle nucleotide polymorphismssex specific |
| spellingShingle | Maral Ranjbar Ruth P. Cusack Christiane E. Whetstone Shiraz Nawaz Christopher Khoury Jennifer Wattie Lesley Wiltshire Jennifer Le Roux Eric Cheng Thivya Srinathan Terence Ho Roma Sehmi MyLinh Duong Gail M. Gauvreau Gene Polymorphisms of Epithelial Cell-Derived Alarmins and Their Effects on Protein Levels and Disease Severity in Patients with COVID-19 Genes COVID-19 severity alarmins single nucleotide polymorphisms sex specific |
| title | Gene Polymorphisms of Epithelial Cell-Derived Alarmins and Their Effects on Protein Levels and Disease Severity in Patients with COVID-19 |
| title_full | Gene Polymorphisms of Epithelial Cell-Derived Alarmins and Their Effects on Protein Levels and Disease Severity in Patients with COVID-19 |
| title_fullStr | Gene Polymorphisms of Epithelial Cell-Derived Alarmins and Their Effects on Protein Levels and Disease Severity in Patients with COVID-19 |
| title_full_unstemmed | Gene Polymorphisms of Epithelial Cell-Derived Alarmins and Their Effects on Protein Levels and Disease Severity in Patients with COVID-19 |
| title_short | Gene Polymorphisms of Epithelial Cell-Derived Alarmins and Their Effects on Protein Levels and Disease Severity in Patients with COVID-19 |
| title_sort | gene polymorphisms of epithelial cell derived alarmins and their effects on protein levels and disease severity in patients with covid 19 |
| topic | COVID-19 severity alarmins single nucleotide polymorphisms sex specific |
| url | https://www.mdpi.com/2073-4425/14/9/1721 |
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