ارتباط پلی‌مورفیسم TRL-9rs352140 و سطوح سرمی پروتئین واکنشگر-c، اینترلوکین-6 و IgG ضد-RBD با شانس ابتلا به سندرم کووید-19 طولانی

نوع مقاله : مقاله های پژوهشی

نویسندگان

1 دانشجوی ژنتیک، گروه زیست‌شناسی، دانشکده‌ی فنی مهندسی و علوم، دانشگاه علم و هنر یزد، یزد، ایران

2 استادیار، گروه ایمنی‎شناسی، دانشکده‌ی پزشکی، دانشگاه علوم پزشکی اصفهان، اصفهان، ایران

3 استادیار، گروه زیست‌شناسی، دانشکده‌ی فنی مهندسی و علوم، دانشگاه علم و هنر یزد، یزد، ایران

4 کارشناسی ارشد، گروه ایمنی‎شناسی، دانشکده‌ی پزشکی، دانشگاه علوم پزشکی اصفهان، اصفهان، ایران

5 استادیار، گروه ژنتیک و بیولوژی مولکولی، دانشکده‌ی پزشکی، دانشگاه علوم پزشکی اصفهان، اصفهان، ایران

10.48305/jims.v43.i814.0470

چکیده

مقاله پژوهشی




مقدمه: سندروم کووید-19 طولانی (Long COVID-19 Syndrome) LCS با علائم متنوع و طولانی، حداقل به‌مدت سه‌ماه پس از مرحله حاد کووید-19، بروز می‎کند. هنوز علل و عوامل خطر مرتبط با LCS بخوبی مشخص نشده ‎است. هدف از این مطالعه، بررسی ارتباط ویژگی‎های جمعیت‌شناختی، سابقه‌ی بستری، شاخص‌های آزمایشگاهی و پلی‌مورفیسم تک‌نوکلئوتیدی 352140rs-9TLR با شانس ابتلا به LCS بود.
روش‌ها: مشخصات جمعیت‌شناختی و سابقه‌ی بستری 88 فرد مبتلا به LCS (گروه LCS+) و 96 فرد بدون LCS (گروه LCS-) از مدارک پزشکی استخراج شد. روش الایزا به‌‎منظور ارزیابی سطوح‎سرمی اینترلوکین-6 (6IL-) و IgG ضد دومن متصل‌شونده به پذیرنده (anti-RBD IgG) و روش ARMS-PCR برای تعیین پلی‌مورفیسم 352140rs-9TLR بکار گرفته شد.
یافته‌ها: فراوانی افراد با سابقه‌ی ابتلا به کووید-19 شدید و همچنین سطوح‌سرمی پروتئین واکنشگر-c (CRP) و 6IL- در گروه LCS+ بطور معنی‌داری بیشتر از گروه LCS- بود (به ترتیب 0/001P ˂ ، 0/005 = P، 0/001 P ˂). علاوه‌ بر آن، فراوانی بیشتری از ژنوتایپ TT و آلل T پلی‌مورفیسم TRL-9rs352140 در گروه LCS+ مشاهده شد (به ترتیب 0/021 = P و 0/002 = P). در مقابل، سطح ‎سرمی anti-RBD IgG و فراوانی ژنوتایپ CC و آلل C در گروه LCS+ کمتر از گروه LCS- بود (به ترتیب 0/001P ˂ ، 010/0 = P و 0/002 = P). آزمون رگرسیون لجستیک‎چندگانه نشان داد که شانس ابتلا به LCS بطور معنی‌داری با سابقه‌ی ابتلا به کووید-19 شدید، سطوح ‌‎سرمی CRP و 6IL- و همچنین با آلل T پلی‌مورفیسم 352140rs-9TLR مرتبط است (به ترتیب 0/001 = P، 0/003 = P، 0/002 = P و 0/018 = P). در حالی‌که، سطح ‎‌سرمی anti-RBD IgG و فراوانی آلل C در ارتباط با محافظت در برابر LCS بود (به ترتیب 0/001P ˂  و 0/018 = P).
نتیجه‌گیری: سابقه‌ی ابتلا به کووید-19 شدید، سطوح‎سرمی 6IL- و CRP، و همچنین حضور آلل T پلیمورفیسم 352140rs-9TLR در ارتباط مستقیم با شانس ابتلا به LCS هستند.

تازه های تحقیق

زینب علوی تبار: Google Scholar, PubMed

حامد فولادسرشت: Google Scholar, PubMed

آمنه جاوید: Google Scholar, PubMed

انسیه ترکی: Google Scholar, PubMed

مجید حسین‌زاده: Google Scholar, PubMed

کلیدواژه‌ها

موضوعات

عنوان مقاله [English]

Association of TLR9-rs352140 Polymorphism and Serum Levels of CRP, IL-6, and Anti-RBD IgG with the Chance of Developing Long COVID-19 Syndrome

نویسندگان [English]

  • Zeynab Alavitabar 1
  • Hamed Fouladseresht 2
  • Amaneh Javid 3
  • Ensiye Torki 4
  • Majid Hosseinzadeh 5
1 Genetics Student, Department of biological sciences, Faculty of Engineering and Science, Science and Art university of Yazd, Yazd, Iran
2 Assistant Professor, Department of Immunology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
3 Assistant Professor, Department of biological sciences, Faculty of Engineering and Science, Science and Art university of Yazd, Yazd, Iran
4 MSc, Department of Immunology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran.
5 Assistant Professor, Department of Genetic and Molecular Biology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
چکیده [English]

Background: Long COVID-19 syndrome (LCS) is characterized by a wide array of symptoms persisting for at least three months after the acute phase of COVID-19. The etiology and risk factors associated with LCS remain poorly understood. This study aimed to investigate the relationship between demographic characteristics, hospitalization history, laboratory parameters, and the TLR9-rs352140 single-nucleotide polymorphism in relation to the risk of developing LCS.
Methods: We collected demographic and hospitalization data from medical records of 88 individuals with LCS (LCS+ group) and 96 without LCS (LCS- group). Serum levels of interleukin-6 (IL-6) and anti-receptor binding domain IgG (anti-RBD IgG) were measured using ELISA, and the TLR9-rs352140 polymorphism was genotyped via ARMS-PCR.
Findings: The LCS+ group showed a significantly higher prevalence of severe COVID-19 history, along with elevated serum levels of C-reactive protein (CRP) and IL-6, compared to the LCS- group (P < 0.001, P = 0.005, and P < 0.001; respectively). Furthermore, the TT genotype and T allele of the TLR9-rs352140 polymorphism were more common in the LCS+ group (P = 0.021 and P = 0.002; respectively). Conversely, the serum level of anti-RBD IgG and the frequency of the CC genotype and C allele were lower (P < 0.001, P = 0.010, and P = 0.002; respectively). Multivariate logistic regression analysis indicated that a history of severe COVID-19, higher CRP and IL-6 levels, and the T allele of TLR9-rs352140 were significantly associated with an increased risk of LCS (P = 0.001, P = 0.003, P = 0.002, and P = 0.018; respectively). While, higher anti-RBD IgG levels and the C allele were linked to a reduced risk of LCS (P < 0.001 and P < 0.018; respectively).
Conclusion: A history of severe COVID-19, higher serum IL-6 and CRP levels, and the T allele of the TLR9-rs352140 polymorphism are positively correlated with the risk of developing LCS.

کلیدواژه‌ها [English]

  • Long COVID
  • Toll-Like Receptor 9
  • C-Reactive Protein
  • Interleukin-6

مراجع

  1. Kerzhner O, Berla E, Har‐Even M, Ratmansky M, Goor‐Aryeh I. Consistency of inconsistency in long‐COVID‐19 pain symptoms persistency: A systematic review and meta‐analysis. Pain Practice 2024; 24(1): 120-59.
  2. Chen C, Haupert SR, Zimmermann L, Shi X, Fritsche LG, Mukherjee B. Global prevalence of post-coronavirus disease 2019 (COVID-19) condition or long COVID: a meta-analysis and systematic review. J Infect Dis 2022; 226(9): 1593-607.
  3. Yong SJ. Long COVID or post-COVID-19 syndrome: putative pathophysiology, risk factors, and treatments. Infect Dis (Lond) 2021; 53(10): 737-54.
  4. Torki E, Gharezade A, Doroudchi M, Sheikhi S, Mansury D, Sullman MJ, et al. The kinetics of inhibitory immune checkpoints during and post-COVID-19: the knowns and unknowns. Clin Exp Med 2023; 23(7): 3299-319.
  5. Torki E, Hoseininasab F, Moradi M, Sami R, Sullman MJ, Fouladseresht H. The demographic, laboratory and genetic factors associated with long COVID-19 syndrome: a case–control study. Clin Exp Med 2024; 24(1): 1.
  6. Perumal R, Shunmugam L, Naidoo K, Abdool Karim SS, Wilkins D, Garzino-Demo A, et al. Long COVID: a review and proposed visualization of the complexity of long COVID. Front Immunol 2023; 14: 1117464.
  7. Notarte KI, Catahay JA, Velasco JV, Pastrana A, Ver AT, Pangilinan FC, et al. Impact of COVID-19 vaccination on the risk of developing long-COVID and on existing long-COVID symptoms: A systematic review. EClinicalMedicine 2022; 53.
  8. Bezemer GF, Garssen J. TLR9 and COVID-19: a multidisciplinary theory of a multifaceted therapeutic target. Front Pharmacol 2021; 11: 601685.
  9. Kumar H, Kawai T, Akira S. Pathogen recognition by the innate immune system. Int Rev Immunol 2011; 30(1): 16-34.
  10. Zhang P, Zhang N, Liu L, Zheng K, Zhu L, Zhu J, et al. Polymorphisms of toll-like receptors 2 and 9 and severity and prognosis of bacterial meningitis in Chinese children. Sci Rep 2017; 7: 42796.
  11. Eed EM, Hawash YA, Khalifa AS, Alsharif KF, Alghamdi SA, Almalki AA, et al. Association of toll-like receptors 2, 4, 9 and 10 genes polymorphisms and Helicobacter pylori-related gastric diseases in Saudi patients. Indian J Med Microbiol 2020; 38(1): 94-100.
  12. Bashir MA, Afzal N, Hamid H, Kashif M, Niaz A, Jahan S. Analysis of single nucleotide polymorphisms encompassing toll like receptor (TLR)-7 (rs179008) and (TLR)-9 (rs352140) in systemic lupus erythematosus patients. Adv Life Sci 2021; 8(2): 103-7.
  13. Wang Y, Xia Y, Chen Y, Xu L, Sun X, Li J, et al. Association analysis between the TLR9 gene polymorphism rs352140 and type 1 diabetes. Front Endocrinol (Lausanne) 2023; 14: 1030736.
  14. O'Mahoney LL, Routen A, Gillies C, Ekezie W, Welford A, Zhang A, et al. The prevalence and long-term health effects of Long Covid among hospitalised and non-hospitalised populations: A systematic review and meta-analysis. EClinicalMedicine 2023; 55: 101762.
  15. Vimercati L, De Maria L, Quarato M, Caputi A, Gesualdo L, Migliore G, et al. Association between long COVID and overweight/obesity. J Clin Med 2021; 10: 4143.
  16. Klöting N, Blüher M. Adipocyte dysfunction, inflammation and metabolic syndrome. Rev Endocr Metab Disord 2014; 15(4): 277-87.
  17. Xiang M, Wu X, Jing H, Novakovic VA, Shi J. The intersection of obesity and (long) COVID-19: Hypoxia, thrombotic inflammation, and vascular endothelial injury. Front Cardiovasc Med 2023; 10: 1062491.
  18. Cervia C, Zurbuchen Y, Taeschler P, Ballouz T, Menges D, Hasler S, et al. Immunoglobulin signature predicts risk of post-acute COVID-19 syndrome. Nat Commun 2022; 13(1): 446.
  19. Asadi-Pooya AA, Akbari A, Emami A, Lotfi M, Rostamihosseinkhani M, Nemati H, et al. Risk factors associated with long COVID syndrome: a retrospective study. Iran J Med Sci 2021; 46(6): 428-36.
  20. Newell KL, Waickman AT. Inflammation, immunity, and antigen persistence in post-acute sequelae of SARS-CoV-2 infection. Curr Opin Immunol 2022; 77: 102228.
  21. Proal AD, VanElzakker MB. Long COVID or post-acute sequelae of COVID-19 (PASC): an overview of biological factors that may contribute to persistent symptoms. Front Microbiol 2021; 12: 698169.
  22. Birra D, Benucci M, Landolfi L, Merchionda A, Loi G, Amato P, et al. COVID 19: a clue from innate immunity. Immunol Res 2020; 68(3): 161-8.
  23. Tang L, Yin Z, Hu Y, Mei H. Controlling cytokine storm is vital in COVID-19. Front Immunol 2020; 11: 570993.
  24. Fouladseresht H, Khazaee S, Javad Zibaeenezhad M, Hossein Nikoo M, Khosropanah S, Doroudchi M. Association of ABCA1 haplotypes with coronary artery disease. Lab Med 2020; 51(2): 157-68.
  25. Rayati Damavandi A, Zolfaghari Baghbadorani P, Kardideh B, Fouladseresht H, Golabi M, Ghezelbash B, et al. The Association of Programmed Death 1 Gene Polymorphisms of PD1. 3 G/A and PD1. 5 C/T with Risk of COVID-19 in an Iranian Population: A Case–Control Study. Viral Immunol 2022; 35: 483-90.
  26. Fouladseresht H, Safa A, Khosropanah S, Doroudchi M. Increased frequency of HLA-A*02 in patients with atherosclerosis is associated with VZV seropositivity. Arch Physiol Biochem 2021; 127(4): 351-8.
  27. Ashchina LA BN, Bolgova AI, Levashova OA, Lesina ON. Prognostic significance of TLR3 and TLR9 gene polymorphism in assessing the severity of COVID-19. Journal Infectology 2024;16(1): 47-55.
  28. Akira S, Hemmi H. Recognition of pathogen-associated molecular patterns by TLR family. Immunol Lett 2003; 85(2): 85-95.
  29. Alhabibi AM, Hassan AS, Abd Elbaky NM, Eid HA, Khalifa MAAA, Wahab MA, et al. Impact of toll-like receptor 2 and 9 gene polymorphisms on COVID-19: susceptibility, severity, and thrombosis. J Inflamm Res 2023; 16: 665-75.
  30. Ng MTH, Van't Hof R, Crockett JC, Hope ME, Berry S, Thomson J, et al. Increase in NF-κB binding affinity of the variant C allele of the Toll-like receptor 9− 1237T/C polymorphism is associated with Helicobacter pylori-induced gastric disease. Infect Immun 2010; 78(3): 1345-52.
  31. Carvalho A, Osorio NS, Saraiva M, Cunha C, Almeida AJ, Teixeira-Coelho M, et al. The C allele of rs5743836 polymorphism in the human TLR9 promoter links IL-6 and TLR9 up-regulation and confers increased B-cell proliferation. PLoS One 2011; 6(11): e28256.
  32. Liu B, Shi Y, Zhang W, Li R, He Z, Yang X, et al. Recovered COVID-19 patients with recurrent viral RNA exhibit lower levels of anti-RBD antibodies. Cell Mol Immunol 2020; 17(10): 1098-100.
  33. Wolszczak-Biedrzycka B, Dorf J, Milewska A, Łukaszyk M, Naumnik W, Kosidło JW, et al. The diagnostic value of inflammatory markers (CRP, IL6, CRP/IL6, CRP/L, LCR) for assessing the severity of COVID-19 symptoms based on the MEWS and predicting the risk of mortality. J Inflamm Res 2023; 16: 2173-88.
  34. Fouladseresht H, Ghamar Talepoor A, Farjadian S, Khosropanah S, Doroudchi M. Anti-varicella Zoster Virus IgG and hsCRP Levels Correlate with Progression of Coronary Artery Atherosclerosis. Iran J Allergy Asthma Immunol 2019; 18(5): 543-53.
مجله دانشکده پزشکی اصفهان
دوره 43، شماره 814
هفته 2، تیر
خرداد و تیر 1404
صفحه 470-480

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  • تاریخ دریافت: 23 اسفند 1403
  • تاریخ پذیرش: 11 تیر 1404

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