Assessing the potential correlation of polymorphisms in the TMPRSS2 gene with severity of COVID 19 patients
Keywords:COVID 19, Gene polymorphism, SARS-CoV-2, TMPRSS2, SNPs
Introduction and Aim: Coronavirus disease (COVID-19) is an infectious disease caused by the SARS-CoV-2 virus. Once infected this virus induces several clinical disorders in humans. SARSCoV-2 enters cells via TMPRSS2. Genetic variation in TMPRSS2 could affect the severity of infection. The purpose of this study was to investigate how the (TMPRSS2) gene polymorphism affected COVID-19 severity in patients as well as the effect of age and comorbidities on infection.
Materials and Methods: This cross-sectional analytical study comprised of 400 (185 male, 215 female) Covid-19-infected patients between ages 18-65 receiving treatment in hospitals at Baghdad, Iraq. The patients were divided into three groups: mild, moderate, and severe based on the severity of Covid-19 infection. Baseline data was collected for each patient through interview and questionnaire. Blood collected from patients was subjected to DNA extraction and detecting polymorphisms within SNPs of the TMPRSS2 gene.
Results: The present investigation indicated higher age to be significantly associated with severe COVID-19 infection when compared to moderate and mild infection (36.14 ± 12.716 vs. 48.52 ± 17.513 vs. 59.26 ± 16.035) (F= 3.697, df: 64, P= 0.000). Patients with comorbidities was associated with a greater rate of severe Covid-19 infection (74.2% vs. 25.8%). However, individuals without comorbidities had a considerably lower rate of mild and moderate Covid-19 infection (13.9% vs. 86.1%) and (36% vs. 64%), respectively (x^2: 97.930, df: 2, P = 0.000). SNPs; (rs383510, rs12329760) within the transmembrane TMPRSS2–7113 was studied and we found no significant (P> 0.05) association for these SNPs to severity of Covid-19 infection.
Conclusion: The results show that the allelic variation within the TMPRSS2 (SNP rs2070788) gene to be linked to increasing illness severity in COVID-19 patients.
Bialek, S., Gierke, R., Hughes, M., McNamara, L.A., Pilishvili, T., Skoff, T. Coronavirus disease 2019 in children—United States. Morbidity and Mortality Weekly Report. 2020; 69(14):422. DOI: https://doi.org/10.15585/mmwr.mm6914e4
Zheng, J. SARS-CoV-2: an emerging coronavirus that causes a global threat. International Journal of Biological Sciences. 2020;16(10):1678. DOI: https://doi.org/10.7150/ijbs.45053
Martinez, M.A. Compounds with therapeutic potential against novel respiratory 2019 coronavirus. Antimicrobial Agents and Chemotherapy. 2020;64(5): e00399-20. DOI: https://doi.org/10.1128/AAC.00399-20
Mousavizadeh, L., Ghasemi, S. Genotype and phenotype of COVID-19: Their roles in pathogenesis. Journal of Microbiology, Immunology and Infection. 2021;54(2):159-163. DOI: https://doi.org/10.1016/j.jmii.2020.03.022
Coronavirus E. 13,968 Cases and 223 Deaths: https://www. worldometers. info/coronavirus/country/Ethiopia. Accessed on. 2020 Jul;27.
Wiersinga, W.J., Rhodes, A., Cheng, A.C., Peacock, S.J., Prescott, H.C. Pathophysiology, transmission, diagnosis, and treatment of coronavirus disease 2019 (COVID-19). a review. JAMA. 2020; 324(8):782-793. DOI: https://doi.org/10.1001/jama.2020.12839
Nersisyan, S., Shkurnikov, M., Turchinovich, A., Knyazev, E. and Tonevitsky, A. Integrative analysis of miRNA and mRNA sequencing data reveals potential regulatory mechanisms of ACE2 and TMPRSS2. PLoS One. 2020; 15(7): e0235987. DOI: https://doi.org/10.1371/journal.pone.0235987
Stopsack, K.H., Mucci, L.A., Antonarakis, E.S., Nelson, P.S., Kantoff, P.W. TMPRSS2 and COVID-19: serendipity or opportunity for intervention? Cancer discovery.2020; 10(6):779-782. DOI: https://doi.org/10.1158/2159-8290.CD-20-0451
Boehmer, T.K., DeVies, J., Caruso, E., van Santen, K.L., Tang, S., Black, C.L., et al., Changing age distribution of the COVID-19 pandemic-United States. Morbidity and Mortality Weekly Report.2020;69(39):1404. DOI: https://doi.org/10.15585/mmwr.mm6939e1
Liu, W., Tao, Z.W., Wang, L., Yuan, M.L., Liu, K., Zhou, L., et al., Analysis of factors associated with disease outcomes in hospitalized patients with 2019 novel coronavirus disease. Chinese Medical Journal.2020;133(09): 1032-1038. DOI: https://doi.org/10.1097/CM9.0000000000000775
Yang, X., Yu, Y., Xu, J., Shu, H., Liu, H., Wu, Y., et al., Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: a single-centered, retrospective, observational study. The Lancet Respiratory Medicine. 2020 May 1;8(5):475-481. DOI: https://doi.org/10.1016/S2213-2600(20)30079-5
Liu, Y., Mao, B., Liang, S., Yang, J.W., Lu, H.W., Chai, Y.H., et al., Association between age and clinical characteristics and outcomes of COVID-19. European Respiratory Journal. 2020;55(5): 1-7; DOI: 10.1183/13993003.01112-2020 DOI: https://doi.org/10.1183/13993003.01112-2020
Lippi, G., Wong, J., Henry, B.M. Hypertension and its severity or mortality in coronavirus disease 2019 (COVID-19): a pooled analysis. Pol Arch Intern Med. 2020;130(4): 304-309. DOI: https://doi.org/10.20452/pamw.15272
Wu, Z., McGoogan, J.M. Characteristics of and important lessons from the coronavirus disease 2019 (COVID-19) outbreak in China: summary of a report of 72 314 cases from the Chinese Center for Disease Control and Prevention. JAMA. 2020;323(13):1239-1242. DOI: https://doi.org/10.1001/jama.2020.2648
Yang, J., Zheng, Y., Gou, X., Pu, K., Chen, Z., Guo, Q., et al., Prevalence of comorbidities in the novel Wuhan coronavirus (COVID-19) infection: a systematic review and meta-analysis. Int J Infect Dis. 2020;94(1):91-95. DOI: https://doi.org/10.1016/j.ijid.2020.03.017
Hou, Y., Zhao, J., Martin, W., Kallianpur, A., Chung, M.K., Jehi, L., et al., New insights into genetic susceptibility of COVID-19: an ACE2 and TMPRSS2 polymorphism analysis. BMC Medicine. 2020;18(1):1-8. DOI: https://doi.org/10.1186/s12916-020-01673-z
Schönfelder, K., Breuckmann, K., Elsner, C., Dittmer, U., Fistera, D., Herbstreit, F., et al., Transmembrane serine protease 2 polymorphisms and susceptibility to severe acute respiratory syndrome coronavirus type 2 infection: a German case-control study. Frontiers in Genetics. 2021 Apr 21;12: 667231. DOI: https://doi.org/10.3389/fgene.2021.667231
Rokni, M., Heidari Nia, M., Sarhadi, M., Mirinejad, S., Sargazi, S., Moudi, M., et al., Association of TMPRSS2 gene polymorphisms with covid-19 severity and mortality: a case-control study with computational analyses. Applied Biochemistry and Biotechnology. 2022; 194: 3507-3526. DOI: https://doi.org/10.1007/s12010-022-03885-w
Vargas-Alarcón, G., Posadas-Sánchez, R., Ramírez-Bello, J. Variability in genes related to SARS-CoV-2 entry into host cells (ACE2, TMPRSS2, TMPRSS11A, ELANE, and CTSL) and its potential use in association studies. Life Sciences. 2020 Nov 1; 260:118313. DOI: https://doi.org/10.1016/j.lfs.2020.118313
Monticelli, M., Hay Mele, B., Benetti, E., Fallerini, C., Baldassarri, M., Furini, S., et al., GEN-COVID multicenter study, protective role of a TMPRSS2 variant on severe COVID-19 outcome in young males and elderly women. Genes. 2021;12(4):596. DOI: https://doi.org/10.3390/genes12040596
Ravaioli, S., Tebaldi, M., Fonzi, E., Angeli, D., Mazza, M., Nicolini, F., et al., ACE2 and TMPRSS2 potential involvement in genetic susceptibility to SARS-COV-2 in cancer patients. Cell Transplantation. 2020 Oct 27; 29:0963689720968749. DOI: https://doi.org/10.1177/0963689720968749
Latini, A., Agolini, E., Novelli, A., Borgiani, P., Giannini, R., Gravina, P., et al., COVID-19 and genetic variants of protein involved in the SARS-CoV-2 entry into the host cells. Genes. 2020;11(9):1010. DOI: https://doi.org/10.3390/genes11091010
Sajuthi, S.P., DeFord, P., Li, Y., Jackson, N.D., Montgomery, M.T., Everman, J.L., et al., Type 2 and interferon inflammation regulate SARS-CoV-2 entry factor expression in the airway epithelium. Nature communications. 2020;11(1):1-8. DOI: https://doi.org/10.1038/s41467-020-18781-2
Asselta, R., Paraboschi, E.M., Mantovani, A., Duga, S. ACE2 and TMPRSS2 variants and expression as candidates to sex and country differences in COVID-19 severity in Italy. Aging (Albany NY). 2020;12(11):10087. DOI: https://doi.org/10.18632/aging.103415
Cheng, Z., Zhou. J., To, K.K., Chu. H., Li, C., Wang, D., et al., Identification of TMPRSS2 as a susceptibility gene for severe 2009 pandemic A (H1N1) influenza and A (H7N9) influenza. The Journal of Infectious Diseases. 2015; 212(8):1214-21. DOI: https://doi.org/10.1093/infdis/jiv246
Vickers, N.J. Animal communication: when I’m calling you, will you answer too? Current Biology. 2017;27(14):713-715. DOI: https://doi.org/10.1016/j.cub.2017.05.064
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