Research Article
Türk Popülasyonunda Çeşitli Doğuştan Bağışıklık Tepkisi Gen Polimorfizmlerinin COVID-19 ile İlişkisi
Abstract
Amaç: Coronavirüs hastalığı 2019 (COVID-19), şiddetli akut solunum sendromu 2 virüsünün (SARS-CoV-2) neden olduğu ve küresel olarak yayıldığı bir hastalıktır. Cinsiyet ve yaş, ciddi COVİD-19 için risk faktörleri olarak belirlenmiştir. Ancak bu faktörler hastalık riski üzerindeki etkileri tam olarak açıklamamaktadır. Araştırmacılara göre, birden fazla gendeki tek nükleotid polimorfizmleri (SNP'ler), COVID-19'un şiddetini etkileyebilir. Viral hastalıkların ilerlemesi hastanın doğuştan gelen bağışıklığının özelliklerine bağlıdır. Doğuştan gelen bağışıklık sisteminin etkinliği, TLR, CCR5 ve RIG-I genlerindeki SNP'ler dahil olmak üzere hastanın genetik faktörlerine bağlıdır. Bu çalışmada, COVID-19 hastalarının SNP'lerindeki alel ve genotip sıklığının yaş ve cinsiyet ile ilişkisini araştırdık.
Gereç ve Yöntem: Çalışmamıza orta şiddette COVİD-19 hastası 200 hasta dahil edildi. TLR3 (rs3775291, rs3775290, rs5743305), TLR7 (rs179008), TLR8 (rs3764880), RIG-I (rs12006123) ve CCR5'in (rs1799987) tek nükleotid polimorfizmleri (SNP) incelenmiştir. SNP'ler, kısıtlama fragmanı uzunluğu polimeraz zincir reaksiyonu (RFLP-PCR) yöntemleriyle belirlendi.
Bulgular: COVID-19 hastalarında allel ve genotip frekansları ile yaş, cinsiyet gibi bazı parametreler arasındaki ilişki açısından değerlendirilen hastaları inceledik. Sonuçlarımızda TLR3 rs5743305 AA genotip frekansı (p=0,03) ve TLR7 rs179008 AA genotip frekansı (p=0,03) yaş ve cinsiyet açısından anlamlı bulundu.
Sonuç: Bu SNP verileri, COVID-19 hastaları için kişiselleştirilmiş farmakolojik tedaviyi planlamak amacıyla hastalık riskine karşı değerlendirilebilir. Bu çalışmadan elde edilecek bulgular genom çapında ilişkilendirme çalışmaları (GWAS) için faydalı olacaktır.
Keywords
Supporting Institution
İKÇÜ BAP
Project Number
2020-COV-TIPF-0002
References
- Hashemi, S.M.A., Thijssen, M., Hosseini, S.Y. et al. Human gene polymorphisms and their possible impact on the outcome of SARS-CoV-2 infection. Arch Virol 166, 2089–2108 (2021). https://doi.org/10.1007/s00705-021-05070-6.
- Madhugiri, R., Fricke, M., Marz, M., & Ziebuhr, J. (2016). Coronavirus cis-Acting RNA Elements. Advances in Virus Research, 127–163. doi:10.1016/bs.aivir.2016.08.007.
- Katze MG, Fornek JL, Palermo RE, Walters KA, Korth MJ. Innate immune modulation by RNA viruses: emerging insights from functional genomics. Nat Rev Immunol. 2008 Aug;8(8):644-54. doi: 10.1038/nri2377. PMID: 18654572; PMCID: PMC7097543.
- Gadanec LK, McSweeney KR, Qaradakhi T, Ali B, Zulli A, Apostolopoulos V. Can SARS-CoV-2 Virus Use Multiple Receptors to Enter Host Cells? Int J Mol Sci. 2021 Jan 20;22(3):992. doi: 10.3390/ijms22030992. PMID: 33498183; PMCID: PMC7863934.
- Salvi, V., Nguyen, H. O., Sozio, F., Schioppa, T., Gaudenzi, C., Laffranchi, M., ... & Bosisio, D. (2021). SARS CoV-2–associated ssRNAs activate inflammation and immunity via TLR7/8. JCI insight, 6(18).Takeuchi, O., & Akira, S. (2007). Recognition of viruses by innate immunity. Immunological Reviews, 220(1), 214–224. doi:10.1111/j.1600-065x.2007.00562.x.
- Lester, S. N., & Li, K. (2014). Toll-Like Receptors in Antiviral Innate Immunity. Journal of Molecular Biology, 426(6), 1246–1264. doi:10.1016/j.jmb.2013.11.024.
- Cao, P., Luo, W.-W., Li, C., Tong, Z., Zheng, Z.-Q., Zhou, L., … Li, S. (2019). The heterogeneous nuclear ribonucleoprotein hnRNPM inhibits RNA virus-triggered innate immunity by antagonizing RNA sensing of RIG I-like receptors. PLOS Pathogens, 15(8), e1007983. doi:10.1371/journal.ppat.1007983.
- Farissi, F. Z., El Annaz, H., El Alaoui, M. A., Elkochri, S., Tagajdid, M. R., Abi, R., … Mrani, S. (2019). Investigation of CCR5-Δ32 (rs333) genetic polymorphism frequency and its relationship with HIV-1 susceptibility and disease progression: A Moroccan case-control study. Gene Reports, 100391. doi:10.1016/j.genrep.2019.100391 10.1016/j.genrep.2019.100391.
- Li, Y., Ke, Y., Xia, X., Wang, Y., Cheng, F., Liu, X., … Zhou, G. (2021). Genome-wide association study of COVID-19 severity among the Chinese population. Cell Discovery, 7(1). doi:10.1038/s41421-021-00318-6.
- Fischer, J., Koukoulioti, E., Schott, E., Fülöp, B., Heyne, R., Berg, T., & van Bömmel, F. (2018). Polymorphisms in the Toll-like receptor 3 (TLR3) gene are associated with the natural course of hepatitis B virus infection in Caucasian population. Scientific Reports, 8(1). doi:10.1038/s41598-018-31065-6.
- Li, Y.-P., Li, M., Jia, X.-L., Deng, H.-L., Wang, W.-J., Wu, F.-P., … Dang, S.-S. (2018). Association of gene polymorphisms of pattern-recognition receptor signaling pathway with the risk and severity of hand, foot, and mouth disease caused by enterovirus 71 in Chinese Han population. Journal of Medical Virology, 90(4), 692 698. doi:10.1002/jmv.25000.
- Alseoudy, M. M., Elgamal, M., Abdelghany, D. A., Borg, A. M., El-Mesery, A., Elzeiny, D., & Hammad, M. O. (2022). Prognostic impact of toll-like receptors gene polymorphism on outcome of COVID-19 pneumonia: A case-control study. Clinical Immunology, 235, 108929.
- Huang X, et al. Genetic polymorphisms in Toll-like receptor 3 gene are associated with the risk of hepatitis B virus-related diseases 10.1016/j.gene.2015.05.054.
- Mosaad YM, Metwally SS, Farag RE, Lotfy ZF, AbdelTwab HE. Association between Toll-Like Receptor 3 (TLR3) rs3775290, TLR7 rs179008, TLR9 rs352140 and Chronic HCV. Immunol Invest. 2019 Apr;48(3):321 332. doi: 10.1080/08820139.2018.1527851. Epub 2018 Oct 15. PMID: 30321082.
- Mukherjee, S., & Tripathi, A. (2019). Contribution of Toll like receptor polymorphisms to dengue susceptibility and clinical outcome among eastern Indian patients. Immunobiology. doi:10.1016/j.imbio.2019.08.009.
- Barkhash, A. V., Voevoda, M. I., & Romaschenko, A. G. (2013). Association of single nucleotide polymorphism rs3775291 in the coding region of the TLR3 gene with predisposition to tick-borne encephalitis in a Russian population. Antiviral Research, 99(2), 136–138. doi:10.1016/j.antiviral.2013.05.008.
- Rong Y et al. (2013) Association of Toll-like receptor 3 polymorphisms with chronic Hepatitis B and Hepatitis B-related acute-on-chronic liver failure. Inflammation 36, 413–418.
- Janett F et al. (2018) Polymorphisms in the Toll-like receptor 3 (TLR3) gene are associated with the natural course of hepatitis B virus infection in Caucasian population. Scientific Reports 8, 12737. Teimouri H, Maali A. Single-nucleotide polymorphisms in host pattern-recognition receptors show association with antiviral responses against SARS-CoV-2, in-silico Trial. J Med Microbiol Infect Dis. 2020;8(2):65–70.
- https://www.genome.jp/pathway/map05171+K05401 (15.11.2023)
- Spiering AE, de Vries TJ. Why Females Do Better: The X Chromosomal TLR7 Gene-Dose Effect in COVID 19. Front Immunol. 2021 Nov 11;12:756262. doi: 10.3389/fimmu.2021.756262. PMID: 34858409; PMCID: PMC8632002.
- Guéry, J. C. (2021). Sex differences in primary HIV infection: revisiting the role of TLR7-driven type 1 IFN production by plasmacytoid dendritic cells in women. Frontiers in Immunology, 12, 729233.
- Bagci G, Gundogdu O, Pektas AN, Bagci B, Avci O, Gursoy S, Kaygusuz K, Elaldi N. The investigation of host genetic variants of toll-like receptor 7 and 8 in COVID-19. Nucleosides Nucleotides Nucleic Acids. 2023;42(8):586-602
- El-Bendary, M., Neamatallah, M., Elalfy, H., Besheer, T., Elkholi, A., El-Diasty, M., … Esmat, G. (2018). The association of single nucleotide polymorphisms of Toll-like receptor 3, Toll-like receptor 7 and Toll-like receptor 8 genes with the susceptibility to HCV infection. British Journal of Biomedical Science, 1–7. doi:10.1080/09674845.2018.1492186.
- Yahya, M. J., Ismail, P. binti, Nordin, N. binti, Akim, A. binti M., Yusuf, W. S. binti M., Adam, N. L. binti, & Yusoff, M. J. (2019). Association of CCL2, CCR5, ELMO1, and IL8 Polymorphism with Diabetic Nephropathy in Malaysian Type 2 Diabetic Patients. International Journal of Chronic Diseases, 2019, 1–13. doi:10.1155/2019/2053015.
- Shieh, B., Liau, Y.-E., Hsieh, P.-S., Yan, Y.-P., Wang, S.-T., & Li, C. (2000). Influence of nucleotide polymorphisms in the CCR2 gene and the CCR5 promoter on the expression of cell surface CCR5 and CXCR4. International Immunology, 12(9), 1311–1318. doi:10.1093/intimm/12.9.1311.
- Mehlotra, R. K. (2020). Chemokine receptor gene polymorphisms and COVID-19: Could knowledge gained from HIV/AIDS be important? Infection, Genetics and Evolution, 85, 104512. doi:10.1016/j.meegid.2020.104512
- Bagci, B., Bagci, G., Huzmeli, C., Sezgin, I., & Ozdemir, O. (2016). Associations of fractalkine receptor (CX3CR1) and CCR5 gene variants with hypertension, diabetes and atherosclerosis in chronic renal failure patients undergoing hemodialysis. International Urology and Nephrology, 48(7), 1163–1170. doi:10.1007/s11255-016-1293-0.
- Clifford, H. D., Yerkovich, S. T., Khoo, S.-K., Zhang, G., Upham, J., Le Souëf, P. N., … Hayden, C. M. (2012). TLR3 and RIG-I gene variants: Associations with functional effects on receptor expression and responses to measles virus and vaccine in vaccinated infants. Human Immunology, 73(6), 677–685. doi:10.1016/j.humimm.2012.03.004.
Association of Several Innate Immune Response Gene Polymorphisms with COVID-19 in Turkish Population
Abstract
Aim: The coronavirus disease 2019 (COVID-19) was caused by severe acute respiratory syndrome 2 virus (SARS-CoV-2), has spread globally. Gender and age have been established as risk factors for severe COVID-19. However, these factors do not fully explain the effects on disease risk. According to researchers, single nucleotide polymorphisms (SNPs) on multiple genes could affect the severity of COVID-19. The progression of viral diseases depends on the characteristics of the patient's innate immunity. The effectiveness of the innate immune system depends on the patient's genetic factors, including SNPs in the TLR, CCR5, and RIG-I genes.
In this study, we researched the association of allele and genotype frequency in SNPs of COVID-19 patients with age and gender.
Materials and Methods: In our study, 200 patients with moderate COVID-19 were included. Single nucleotide polymorphisms (SNP) of TLR3 (rs3775291, rs3775290, rs5743305), TLR7 (rs179008), TLR8 (rs3764880), RIG-I (rs12006123), and CCR5 (rs1799987) were studied. SNPs were determined by restriction fragment length polymerase chain reaction (RFLP-PCR) methods.
Results: In the COVID-19 patients, we examined the patients were evaluated in terms of allele and genotype frequencies and the association between some parameters like age, and gender. In our results, TLR3 rs5743305 AA genotype frequency (p=0.03) and TLR7 rs179008 AA genotype frequency (p=0.03) were found to be significant in terms of age and gender.
Conclusions: These SNP data is assessed against disease risk to plan personalized pharmacological therapy for COVID-19 patients.The findings from this study will be useful for genome-wide association studies (GWAS).
Keywords
Project Number
2020-COV-TIPF-0002
References
- Hashemi, S.M.A., Thijssen, M., Hosseini, S.Y. et al. Human gene polymorphisms and their possible impact on the outcome of SARS-CoV-2 infection. Arch Virol 166, 2089–2108 (2021). https://doi.org/10.1007/s00705-021-05070-6.
- Madhugiri, R., Fricke, M., Marz, M., & Ziebuhr, J. (2016). Coronavirus cis-Acting RNA Elements. Advances in Virus Research, 127–163. doi:10.1016/bs.aivir.2016.08.007.
- Katze MG, Fornek JL, Palermo RE, Walters KA, Korth MJ. Innate immune modulation by RNA viruses: emerging insights from functional genomics. Nat Rev Immunol. 2008 Aug;8(8):644-54. doi: 10.1038/nri2377. PMID: 18654572; PMCID: PMC7097543.
- Gadanec LK, McSweeney KR, Qaradakhi T, Ali B, Zulli A, Apostolopoulos V. Can SARS-CoV-2 Virus Use Multiple Receptors to Enter Host Cells? Int J Mol Sci. 2021 Jan 20;22(3):992. doi: 10.3390/ijms22030992. PMID: 33498183; PMCID: PMC7863934.
- Salvi, V., Nguyen, H. O., Sozio, F., Schioppa, T., Gaudenzi, C., Laffranchi, M., ... & Bosisio, D. (2021). SARS CoV-2–associated ssRNAs activate inflammation and immunity via TLR7/8. JCI insight, 6(18).Takeuchi, O., & Akira, S. (2007). Recognition of viruses by innate immunity. Immunological Reviews, 220(1), 214–224. doi:10.1111/j.1600-065x.2007.00562.x.
- Lester, S. N., & Li, K. (2014). Toll-Like Receptors in Antiviral Innate Immunity. Journal of Molecular Biology, 426(6), 1246–1264. doi:10.1016/j.jmb.2013.11.024.
- Cao, P., Luo, W.-W., Li, C., Tong, Z., Zheng, Z.-Q., Zhou, L., … Li, S. (2019). The heterogeneous nuclear ribonucleoprotein hnRNPM inhibits RNA virus-triggered innate immunity by antagonizing RNA sensing of RIG I-like receptors. PLOS Pathogens, 15(8), e1007983. doi:10.1371/journal.ppat.1007983.
- Farissi, F. Z., El Annaz, H., El Alaoui, M. A., Elkochri, S., Tagajdid, M. R., Abi, R., … Mrani, S. (2019). Investigation of CCR5-Δ32 (rs333) genetic polymorphism frequency and its relationship with HIV-1 susceptibility and disease progression: A Moroccan case-control study. Gene Reports, 100391. doi:10.1016/j.genrep.2019.100391 10.1016/j.genrep.2019.100391.
- Li, Y., Ke, Y., Xia, X., Wang, Y., Cheng, F., Liu, X., … Zhou, G. (2021). Genome-wide association study of COVID-19 severity among the Chinese population. Cell Discovery, 7(1). doi:10.1038/s41421-021-00318-6.
- Fischer, J., Koukoulioti, E., Schott, E., Fülöp, B., Heyne, R., Berg, T., & van Bömmel, F. (2018). Polymorphisms in the Toll-like receptor 3 (TLR3) gene are associated with the natural course of hepatitis B virus infection in Caucasian population. Scientific Reports, 8(1). doi:10.1038/s41598-018-31065-6.
- Li, Y.-P., Li, M., Jia, X.-L., Deng, H.-L., Wang, W.-J., Wu, F.-P., … Dang, S.-S. (2018). Association of gene polymorphisms of pattern-recognition receptor signaling pathway with the risk and severity of hand, foot, and mouth disease caused by enterovirus 71 in Chinese Han population. Journal of Medical Virology, 90(4), 692 698. doi:10.1002/jmv.25000.
- Alseoudy, M. M., Elgamal, M., Abdelghany, D. A., Borg, A. M., El-Mesery, A., Elzeiny, D., & Hammad, M. O. (2022). Prognostic impact of toll-like receptors gene polymorphism on outcome of COVID-19 pneumonia: A case-control study. Clinical Immunology, 235, 108929.
- Huang X, et al. Genetic polymorphisms in Toll-like receptor 3 gene are associated with the risk of hepatitis B virus-related diseases 10.1016/j.gene.2015.05.054.
- Mosaad YM, Metwally SS, Farag RE, Lotfy ZF, AbdelTwab HE. Association between Toll-Like Receptor 3 (TLR3) rs3775290, TLR7 rs179008, TLR9 rs352140 and Chronic HCV. Immunol Invest. 2019 Apr;48(3):321 332. doi: 10.1080/08820139.2018.1527851. Epub 2018 Oct 15. PMID: 30321082.
- Mukherjee, S., & Tripathi, A. (2019). Contribution of Toll like receptor polymorphisms to dengue susceptibility and clinical outcome among eastern Indian patients. Immunobiology. doi:10.1016/j.imbio.2019.08.009.
- Barkhash, A. V., Voevoda, M. I., & Romaschenko, A. G. (2013). Association of single nucleotide polymorphism rs3775291 in the coding region of the TLR3 gene with predisposition to tick-borne encephalitis in a Russian population. Antiviral Research, 99(2), 136–138. doi:10.1016/j.antiviral.2013.05.008.
- Rong Y et al. (2013) Association of Toll-like receptor 3 polymorphisms with chronic Hepatitis B and Hepatitis B-related acute-on-chronic liver failure. Inflammation 36, 413–418.
- Janett F et al. (2018) Polymorphisms in the Toll-like receptor 3 (TLR3) gene are associated with the natural course of hepatitis B virus infection in Caucasian population. Scientific Reports 8, 12737. Teimouri H, Maali A. Single-nucleotide polymorphisms in host pattern-recognition receptors show association with antiviral responses against SARS-CoV-2, in-silico Trial. J Med Microbiol Infect Dis. 2020;8(2):65–70.
- https://www.genome.jp/pathway/map05171+K05401 (15.11.2023)
- Spiering AE, de Vries TJ. Why Females Do Better: The X Chromosomal TLR7 Gene-Dose Effect in COVID 19. Front Immunol. 2021 Nov 11;12:756262. doi: 10.3389/fimmu.2021.756262. PMID: 34858409; PMCID: PMC8632002.
- Guéry, J. C. (2021). Sex differences in primary HIV infection: revisiting the role of TLR7-driven type 1 IFN production by plasmacytoid dendritic cells in women. Frontiers in Immunology, 12, 729233.
- Bagci G, Gundogdu O, Pektas AN, Bagci B, Avci O, Gursoy S, Kaygusuz K, Elaldi N. The investigation of host genetic variants of toll-like receptor 7 and 8 in COVID-19. Nucleosides Nucleotides Nucleic Acids. 2023;42(8):586-602
- El-Bendary, M., Neamatallah, M., Elalfy, H., Besheer, T., Elkholi, A., El-Diasty, M., … Esmat, G. (2018). The association of single nucleotide polymorphisms of Toll-like receptor 3, Toll-like receptor 7 and Toll-like receptor 8 genes with the susceptibility to HCV infection. British Journal of Biomedical Science, 1–7. doi:10.1080/09674845.2018.1492186.
- Yahya, M. J., Ismail, P. binti, Nordin, N. binti, Akim, A. binti M., Yusuf, W. S. binti M., Adam, N. L. binti, & Yusoff, M. J. (2019). Association of CCL2, CCR5, ELMO1, and IL8 Polymorphism with Diabetic Nephropathy in Malaysian Type 2 Diabetic Patients. International Journal of Chronic Diseases, 2019, 1–13. doi:10.1155/2019/2053015.
- Shieh, B., Liau, Y.-E., Hsieh, P.-S., Yan, Y.-P., Wang, S.-T., & Li, C. (2000). Influence of nucleotide polymorphisms in the CCR2 gene and the CCR5 promoter on the expression of cell surface CCR5 and CXCR4. International Immunology, 12(9), 1311–1318. doi:10.1093/intimm/12.9.1311.
- Mehlotra, R. K. (2020). Chemokine receptor gene polymorphisms and COVID-19: Could knowledge gained from HIV/AIDS be important? Infection, Genetics and Evolution, 85, 104512. doi:10.1016/j.meegid.2020.104512
- Bagci, B., Bagci, G., Huzmeli, C., Sezgin, I., & Ozdemir, O. (2016). Associations of fractalkine receptor (CX3CR1) and CCR5 gene variants with hypertension, diabetes and atherosclerosis in chronic renal failure patients undergoing hemodialysis. International Urology and Nephrology, 48(7), 1163–1170. doi:10.1007/s11255-016-1293-0.
- Clifford, H. D., Yerkovich, S. T., Khoo, S.-K., Zhang, G., Upham, J., Le Souëf, P. N., … Hayden, C. M. (2012). TLR3 and RIG-I gene variants: Associations with functional effects on receptor expression and responses to measles virus and vaccine in vaccinated infants. Human Immunology, 73(6), 677–685. doi:10.1016/j.humimm.2012.03.004.
There are 28 citations in total.
Details
| Primary Language | English |
|---|---|
| Subjects | Basic Immunology |
| Journal Section | Research Articles |
| Authors | |
| Project Number | 2020-COV-TIPF-0002 |
| Publication Date | June 10, 2024 |
| Submission Date | September 7, 2023 |
| Published in Issue | Year 2024 |