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Strong association between COVID-19 and Single Nucleotide Polymorphism in Nuclear Factor Kappa B genes

Yıl 2025, Cilt: 10 Sayı: 1, 15 - 21
https://doi.org/10.26453/otjhs.1505688

Öz

Objectives: SARS-CoV-2 is an enveloped, positive-sense, single-stranded RNA virus belonging to the Betacoronavirus genus. This study aimed to investigate the relationship between COVID-19 severity and NF-κB1 -94 ins/del (rs28362491), NF-κB1A 3’UTR A/G (rs696), -826 C/T (rs2233406) polymorphisms.
Materials and Methods: We investigated the frequencies of these gene polymorphisms in 150 patients with COVID-19 and 171 healthy controls. Total DNA was isolated from the blood samples, and then the PCR-RFLP study was used for genotyping. All statistical analyses were calculated using the chi-square method using SPSS.
Results: A statistically significant differences were determined in the D allele frequency, WD and DD genotype frequencies for the rs28362491 polymorphism. For rs696 polymorphism, there was a statistically significant difference in the frequency of the G allele of patients with COVID-19. Additionally, for this polymorphism, CT and TT genotype frequencies were shown to be statistically significant. It was also found that the T allele, CT, and TT genotype frequencies for the rs2233406 have a statistically significant difference.
Conclusion: A significant association was found between COVID-19 disease and NF-κB genes, but further studies, such as investigating promoter activity or gene expression levels, are needed.

Proje Numarası

F-2021-635

Kaynakça

  • 1. Bhat EA, Khan J, Sajjad N, et al. SARS-CoV-2: Insight in genome structure, pathogenesis and viral receptor binding analysis - An updated review. Int Immunopharmacol. 2021;95:107493. doi:10.1016/j.intimp.2021.107493
  • 2. Lu R, Zhao X, Li J, et al. Genomic characterization and epidemiology of 2019 novel coronavirus: Implications for virus origins and receptor binding. Lancet. 2020;395(10224):565-574. doi:10.1016/S0140-6736(20)30251-8
  • 3. Hu B, Guo H, Zhou P, Shi ZL. Characteristics of SARS-CoV-2 and COVID-19. Nat Rev Microbiol. 2021;19(3):141-154. doi:10.1038/s41579-020-00459-7
  • 4. Chowdhury MA, Hossain N, Kashem MA, Shahid MA, Alam A. Immune response in COVID-19: A review. J Infect Public Health. 2020;13(11):1619-1629. doi:10.1016/j.jiph.2020.07.001
  • 5. Gudowska-Sawczuk M, Mroczko B. What is currently known about the role of CXCL10 in SARS-CoV-2 infection? Int J Mol Sci. 2022;23(7):3673. doi:10.3390/ijms23073673
  • 6. Liu T, Zhang L, Joo D, Sun SC. NF-κB signalling in inflammation. Signal Transduct Target Ther. 2017;2:17023. doi:10.1038/sigtrans.2017.23
  • 7. Hayden MS, Ghosh S. Shared principles in NF-kappaB signaling. Cell. 2008;132(3):344-362. doi:10.1016/j.cell.2008.01.020
  • 8. Lin CW, Hsieh YS, Hsin CH, et al. Effects of NFKB1 and NFKBIA gene polymorphisms on susceptibility to environmental factors and the clinicopathologic development of oral cancer. PLoS One. 2012;7(4):e35078.
  • 9. He Y, Zhang H, Yin J, et al. Ikappa Balpha gene promoter polymorphisms are associated with hepatocarcinogenesis in patients infected with hepatitis B virus genotype C. Carcinogenesis. 2009;30(11):1916-1922. doi:10.1093/carcin/bgp226
  • 10. Glavac D, Ravnik-Glavac M, O'Brien SJ, Dean M. Polymorphisms in the 3' untranslated region of the I kappa B/MAD-3 (NFKBI) gene located on chromosome 14. Hum Genet. 1994;93(6):694-696. doi:10.1007/BF00201573
  • 11. Gao J, Pfeifer D, He LJ, et al. Association of NFKBIA polymorphism with colorectal cancer risk and prognosis in Swedish and Chinese populations. Scand J Gastroenterol. 2007;42(3):345-350. doi:10.1080/00365520600880856
  • 12. Sambrook J, Westphal H, Srinivasan PR, Dulbecco R. The integrated state of viral DNA in SV40-transformed cells. Proc Natl Acad Sci. 1968;60(4):1288-1295.
  • 13. Arslan S, Engin A. Relationship between NF-κB1 and NF-κBIA genetic polymorphisms and Crimean-Congo hemorrhagic fever. Scand J Infect Dis. 2012;44(2):138-143. doi:10.3109/00365548.2011.623313
  • 14. Özbilüm N, Arslan S, Berkan Ö, Yanartaş M, Aydemir EI. The role of NF-κB1A promoter polymorphisms on coronary artery disease risk. Basic Clin Pharmacol Toxicol. 2013;113(3):187-192. doi:10.1111/bcpt.12085
  • 15. Hariharan A, Hakeem AR, Radhakrishnan S, Reddy MS, Rela M. The role and therapeutic potential of NF-kappa-B pathway in severe COVID-19 patients. Inflammopharmacology. 2021;29(1):91-100. doi:10.1007/s10787-020-00773-9
  • 16. Liao QJ, Ye LB, Timani KA, et al. Activation of NF-kappaB by the full-length nucleocapsid protein of the SARS coronavirus. Acta Biochim Biophys Sin (Shanghai). 2005;37(9):607-612.
  • 17. Farahani M, Niknam Z, Mohammadi Amirabad L, et al. Molecular pathways involved in COVID-19 and potential pathway-based therapeutic targets. Biomed Pharmacother. 2022;145:112420. doi:10.1111/j.1745-7270.2005.00082.x
  • 18. Zhang P, Wei Q, Li X, et al. A functional insertion/deletion polymorphism in the promoter region of the NFKB1 gene increases susceptibility for prostate cancer. Cancer Genet Cytogenet. 2009;191(2):73-77.
  • 19. Urbanowicz I, Wołowiec D, Wysoczańska B, et al. NF-κB1 -94del/del ATTG polymorphic variant maintains CLL at an early, mildest stage. Adv Clin Exp Med. 2021;30(5):499-506. doi:10.17219/acem/128764
  • 20. Chatterjee T, De D, Chowdhury S, Bhattacharyya M. Nuclear factor NF-κB1 functional promoter polymorphism and its expression conferring the risk of Type 2 diabetes-associated dyslipidemia. Mamm Genome. 2020;31(7-8):252-262. doi:10.1007/s00335-020-09846-0
  • 21. Wang X, Peng H, Liang Y, et al. A functional insertion/deletion polymorphism in the promoter region of the NFKB1 gene increases the risk of papillary thyroid carcinoma. Genet Test Mol Biomarkers. 2015;19(3):167-171. doi:10.1089/gtmb.2014.0271
  • 22. Fan HZ, Huang P, Shao JG, et al. Genetic variation on the NFKB1 genes associates with the outcomes of HCV infection among Chinese Han population. Infect Genet Evol. 2018;65:210-215. doi:10.1016/j.meegid.2018.07.031
  • 23. Fakhir FZ, Lkhider M, Badre W, et al. The -94Ins/DelATTG polymorphism in NFκB1 promoter modulates chronic hepatitis C and liver disease progression. Infect Genet Evol. 2016;39:141-146.
  • 24. Simonian M, Mosallayi M, Miraghajani M, et al. Single nucleotide polymorphism rs696 in miR449a binding site of NFKBIA gene is correlated with risk of colorectal cancer. Gastroenterol Hepatol Bed Bench. 2018;11(1):48-53.
  • 25. Camblor DG, Miranda D, Albaiceta GM, et al. Genetic variants in the NF-κB signaling pathway (NFKB1, NFKBIA, NFKBIZ) and risk of critical outcome among COVID-19 patients. Hum Immunol. 2022;83(8-9):613-617. doi:10.1016/j.humimm.2022.06.002
  • 26. Ravindra NG, Alfajaro MM, Gasque V, et al. Single-cell longitudinal analysis of SARS-CoV-2 infection in human airway epithelium identifies target cells, alterations in gene expression, and cell state changes. PLoS Biol. 2021;19(3):e3001143. doi:10.1371/journal.pbio.3001143
  • 27. Mourad R, Hsu PY, Juan L, et al. Estrogen induces global reorganization of chromatin structure in human breast cancer cells. PLoS One. 2014;9(12):e113354. doi:10.1371/journal.pone.0113354
  • 28. Zhang M, Huang J, Tan X, et al. Common polymorphisms in the NFKBIA gene and cancer susceptibility: A meta-analysis. Med Sci Monit. 2015;21:3186-3196. doi:10.12659/MSM.895257
  • 29. Plantinga TS, Petrulea MS, Oosting M, et al. Association of NF-κB polymorphisms with clinical outcome of non-medullary thyroid carcinoma. Endocr Relat Cancer. 2017;24(7):307-318. doi:10.1530/ERC-17-0033
  • 30. Zhang GL, Zou YF, Feng XL, et al. Association of the NFKBIA gene polymorphisms with susceptibility to autoimmune and inflammatory diseases: A meta-analysis. Inflamm Res. 2011;60(1):11-18. doi:10.1007/s00011-010-0216-2

COVID-19 ile Nükleer Faktör Kappa B Genlerindeki Tek Nükleotid Polimorfizmleri Arasındaki Güçlü Bir İlişki

Yıl 2025, Cilt: 10 Sayı: 1, 15 - 21
https://doi.org/10.26453/otjhs.1505688

Öz

Amaç: SARS-CoV-2, Betacoronavirus cinsine ait zarflı, pozitif polariteli, tek sarmallı bir RNA virüsüdür. Bu çalışmada COVID-19 hastalığının şiddeti ve NF-κB1 -94 ins/del (rs28362491), NF-κB1A 3’UTR A/G (rs696), NFk-B1A -826 C/T (rs2233406) polimorfizmleri arasındaki ilişkinin araştırılması amaçlanmıştır.
Gereç ve Yöntem: COVID-19'lu 150 hastada ve kontrol olarak 171 sağlıklı bireyde bu genlerin polimorfizm sıklıklarını araştırdık. Kan örneklerinden total DNA izole edildi ve ardından genotipleme için PCR-RFLP çalışması kullanıldı. Tüm istatistiki analizler SPSS kullanılarak ki-kare yöntemi ile hesaplanmıştır.
Bulgular: Rs28362491 polimorfizmi için D alel frekansı, WD ve DD genotip frekanslarında istatistiksel olarak anlamlı farklılıklar tespit edilmiştir. Rs696 polimorfizmi için, COVID-19'lu hastaların G aleli sıklığında istatistiksel olarak anlamlı bir fark vardı. Ayrıca, bu polimorfizm için CT ve TT genotip frekanslarının istatistiksel olarak anlamlı olduğu gösterilmiştir. Ayrıca, rs2233406 için T aleli, CT ve TT genotip frekanslarının istatistiksel olarak anlamlı bir farka sahip olduğu bulunmuştur.
Sonuç: COVID-19 hastalığı ile NF-κB genleri arasında anlamlı bir ilişki bulunmuştur, ancak promotör aktivitesinin veya gen ekspresyon seviyelerinin araştırılması gibi daha ileri çalışmalara ihtiyaç vardır.

Proje Numarası

F-2021-635

Kaynakça

  • 1. Bhat EA, Khan J, Sajjad N, et al. SARS-CoV-2: Insight in genome structure, pathogenesis and viral receptor binding analysis - An updated review. Int Immunopharmacol. 2021;95:107493. doi:10.1016/j.intimp.2021.107493
  • 2. Lu R, Zhao X, Li J, et al. Genomic characterization and epidemiology of 2019 novel coronavirus: Implications for virus origins and receptor binding. Lancet. 2020;395(10224):565-574. doi:10.1016/S0140-6736(20)30251-8
  • 3. Hu B, Guo H, Zhou P, Shi ZL. Characteristics of SARS-CoV-2 and COVID-19. Nat Rev Microbiol. 2021;19(3):141-154. doi:10.1038/s41579-020-00459-7
  • 4. Chowdhury MA, Hossain N, Kashem MA, Shahid MA, Alam A. Immune response in COVID-19: A review. J Infect Public Health. 2020;13(11):1619-1629. doi:10.1016/j.jiph.2020.07.001
  • 5. Gudowska-Sawczuk M, Mroczko B. What is currently known about the role of CXCL10 in SARS-CoV-2 infection? Int J Mol Sci. 2022;23(7):3673. doi:10.3390/ijms23073673
  • 6. Liu T, Zhang L, Joo D, Sun SC. NF-κB signalling in inflammation. Signal Transduct Target Ther. 2017;2:17023. doi:10.1038/sigtrans.2017.23
  • 7. Hayden MS, Ghosh S. Shared principles in NF-kappaB signaling. Cell. 2008;132(3):344-362. doi:10.1016/j.cell.2008.01.020
  • 8. Lin CW, Hsieh YS, Hsin CH, et al. Effects of NFKB1 and NFKBIA gene polymorphisms on susceptibility to environmental factors and the clinicopathologic development of oral cancer. PLoS One. 2012;7(4):e35078.
  • 9. He Y, Zhang H, Yin J, et al. Ikappa Balpha gene promoter polymorphisms are associated with hepatocarcinogenesis in patients infected with hepatitis B virus genotype C. Carcinogenesis. 2009;30(11):1916-1922. doi:10.1093/carcin/bgp226
  • 10. Glavac D, Ravnik-Glavac M, O'Brien SJ, Dean M. Polymorphisms in the 3' untranslated region of the I kappa B/MAD-3 (NFKBI) gene located on chromosome 14. Hum Genet. 1994;93(6):694-696. doi:10.1007/BF00201573
  • 11. Gao J, Pfeifer D, He LJ, et al. Association of NFKBIA polymorphism with colorectal cancer risk and prognosis in Swedish and Chinese populations. Scand J Gastroenterol. 2007;42(3):345-350. doi:10.1080/00365520600880856
  • 12. Sambrook J, Westphal H, Srinivasan PR, Dulbecco R. The integrated state of viral DNA in SV40-transformed cells. Proc Natl Acad Sci. 1968;60(4):1288-1295.
  • 13. Arslan S, Engin A. Relationship between NF-κB1 and NF-κBIA genetic polymorphisms and Crimean-Congo hemorrhagic fever. Scand J Infect Dis. 2012;44(2):138-143. doi:10.3109/00365548.2011.623313
  • 14. Özbilüm N, Arslan S, Berkan Ö, Yanartaş M, Aydemir EI. The role of NF-κB1A promoter polymorphisms on coronary artery disease risk. Basic Clin Pharmacol Toxicol. 2013;113(3):187-192. doi:10.1111/bcpt.12085
  • 15. Hariharan A, Hakeem AR, Radhakrishnan S, Reddy MS, Rela M. The role and therapeutic potential of NF-kappa-B pathway in severe COVID-19 patients. Inflammopharmacology. 2021;29(1):91-100. doi:10.1007/s10787-020-00773-9
  • 16. Liao QJ, Ye LB, Timani KA, et al. Activation of NF-kappaB by the full-length nucleocapsid protein of the SARS coronavirus. Acta Biochim Biophys Sin (Shanghai). 2005;37(9):607-612.
  • 17. Farahani M, Niknam Z, Mohammadi Amirabad L, et al. Molecular pathways involved in COVID-19 and potential pathway-based therapeutic targets. Biomed Pharmacother. 2022;145:112420. doi:10.1111/j.1745-7270.2005.00082.x
  • 18. Zhang P, Wei Q, Li X, et al. A functional insertion/deletion polymorphism in the promoter region of the NFKB1 gene increases susceptibility for prostate cancer. Cancer Genet Cytogenet. 2009;191(2):73-77.
  • 19. Urbanowicz I, Wołowiec D, Wysoczańska B, et al. NF-κB1 -94del/del ATTG polymorphic variant maintains CLL at an early, mildest stage. Adv Clin Exp Med. 2021;30(5):499-506. doi:10.17219/acem/128764
  • 20. Chatterjee T, De D, Chowdhury S, Bhattacharyya M. Nuclear factor NF-κB1 functional promoter polymorphism and its expression conferring the risk of Type 2 diabetes-associated dyslipidemia. Mamm Genome. 2020;31(7-8):252-262. doi:10.1007/s00335-020-09846-0
  • 21. Wang X, Peng H, Liang Y, et al. A functional insertion/deletion polymorphism in the promoter region of the NFKB1 gene increases the risk of papillary thyroid carcinoma. Genet Test Mol Biomarkers. 2015;19(3):167-171. doi:10.1089/gtmb.2014.0271
  • 22. Fan HZ, Huang P, Shao JG, et al. Genetic variation on the NFKB1 genes associates with the outcomes of HCV infection among Chinese Han population. Infect Genet Evol. 2018;65:210-215. doi:10.1016/j.meegid.2018.07.031
  • 23. Fakhir FZ, Lkhider M, Badre W, et al. The -94Ins/DelATTG polymorphism in NFκB1 promoter modulates chronic hepatitis C and liver disease progression. Infect Genet Evol. 2016;39:141-146.
  • 24. Simonian M, Mosallayi M, Miraghajani M, et al. Single nucleotide polymorphism rs696 in miR449a binding site of NFKBIA gene is correlated with risk of colorectal cancer. Gastroenterol Hepatol Bed Bench. 2018;11(1):48-53.
  • 25. Camblor DG, Miranda D, Albaiceta GM, et al. Genetic variants in the NF-κB signaling pathway (NFKB1, NFKBIA, NFKBIZ) and risk of critical outcome among COVID-19 patients. Hum Immunol. 2022;83(8-9):613-617. doi:10.1016/j.humimm.2022.06.002
  • 26. Ravindra NG, Alfajaro MM, Gasque V, et al. Single-cell longitudinal analysis of SARS-CoV-2 infection in human airway epithelium identifies target cells, alterations in gene expression, and cell state changes. PLoS Biol. 2021;19(3):e3001143. doi:10.1371/journal.pbio.3001143
  • 27. Mourad R, Hsu PY, Juan L, et al. Estrogen induces global reorganization of chromatin structure in human breast cancer cells. PLoS One. 2014;9(12):e113354. doi:10.1371/journal.pone.0113354
  • 28. Zhang M, Huang J, Tan X, et al. Common polymorphisms in the NFKBIA gene and cancer susceptibility: A meta-analysis. Med Sci Monit. 2015;21:3186-3196. doi:10.12659/MSM.895257
  • 29. Plantinga TS, Petrulea MS, Oosting M, et al. Association of NF-κB polymorphisms with clinical outcome of non-medullary thyroid carcinoma. Endocr Relat Cancer. 2017;24(7):307-318. doi:10.1530/ERC-17-0033
  • 30. Zhang GL, Zou YF, Feng XL, et al. Association of the NFKBIA gene polymorphisms with susceptibility to autoimmune and inflammatory diseases: A meta-analysis. Inflamm Res. 2011;60(1):11-18. doi:10.1007/s00011-010-0216-2
Toplam 30 adet kaynakça vardır.

Ayrıntılar

Birincil Dil İngilizce
Konular Biyokimya ve Hücre Biyolojisi (Diğer), Tıbbi Enfeksiyon Ajanları
Bölüm Araştırma Makalesi
Yazarlar

Nil Özbilüm 0000-0002-2889-3600

Burcu Bayyurt 0000-0002-5618-457X

Sevgi Baltacı 0000-0002-2466-777X

Mehmet Bakır 0000-0003-3702-1932

Serdal Arslan 0000-0002-3921-8061

Proje Numarası F-2021-635
Erken Görünüm Tarihi 10 Mart 2025
Yayımlanma Tarihi
Gönderilme Tarihi 27 Haziran 2024
Kabul Tarihi 18 Aralık 2024
Yayımlandığı Sayı Yıl 2025 Cilt: 10 Sayı: 1

Kaynak Göster

AMA Özbilüm N, Bayyurt B, Baltacı S, Bakır M, Arslan S. Strong association between COVID-19 and Single Nucleotide Polymorphism in Nuclear Factor Kappa B genes. OTSBD. Mart 2025;10(1):15-21. doi:10.26453/otjhs.1505688

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