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Abstract

Introduction: COVID-19 is a new type of coronavirus that infects humans and causes severe acute respiratory syndrome (SARS). Isolated in Wuhan City, China, in December 2019. Similar to discoveries relating to the coronaviruses that cause severe acute respiratory syndrome (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV). Levels of cytokines (Interleukin-6, Interleukin-1 β ), iron and hemoglobin changed during COVID-19 disease. Hepcidin is an iron regulatory protein that is encoded by the HAMP gene . 


Material and Methods : Serum IL-6, IL-1 β , Hepcidin are measured by an ELISA kit and Iron ,UIBC , TIBC are measured by colorimetric methods. The genotyping was done by the ARM-PCR technique with a specific set of primers.


Results : The difference in Hb and serum iron levels, UIBC, TIBC, IL-1, IL-6, and Hepcidin conc. between the patient and recovery groups is statistically significant at P≤ 0.05 . No significant difference between the two groups in hepcidin gene polymorphism because of Polymorphisms of the hepcidin gene appeared in the two groups (in most samples).


Conclusions: The persons  involved in this study are (most of them) heterozygous, and this indicates the presence of the mutation allele in the two groups , and it may be one of the reasons for the deficiency in hepcidin that appeared in this study.

Keywords

HAMP gene , coronavirus , IL-6 , IL-1 beta ,Hemoglobin , Iron parameter .

Article Details

How to Cite
H. Salem , M. ., A. Jabir , F. ., & A. Jabir , F. . (2022). Association Of Hepcidin (HAMP) Gene Polymorphism And Cytokines, Iron, And Hb Levels In Covid-19 Patients . Medical Science Journal for Advance Research, 3(3), 107–115. https://doi.org/10.46966/msjar.v3i3.50

References

  1. Zhu N, Zhang D, Wang W, Li X, Yang B and Song J, et al. A Novel Coronavirus from Patients with Pneumonia in China, 2019. N Engl J Med. 2020;382(8):727–33.
  2. Velavan TP, Meyer CG. The COVID-19 epidemic. Trop Med Int Heal. 2020;25(3):278–80.
  3. Shi Y, Wang G, Cai X, Deng J, Zheng L, Zhu H, et al. An overview of COVID-19. 2020;21(5):343–60.
  4. Tyrrell DAJ. Cultivation of " Difficult " Viruses from Patients with Common Colds. 1968; 606–10.
  5. Xu X, Wu X, Jiang X, Xu K, Ying L, Ma C, et al. Clinical findings in a group of patients infected with the 2019 novel coronavirus ( SARS-Cov-2 ) outside of Wuhan , China : retrospective case series. 2020;2019:1–7.
  6. Agarwal AK, Yee J. Hepcidin. Adv Chronic Kidney Dis. 2019;26(4):298–305.
  7. Pandur E, Sipos K, Grama L, Nagy J, Poór VS, Sétáló G, et al. Prohepcidin binds to the HAMP promoter and autoregulates its own expression. Biochem J. 2013;451(2):301–11.
  8. Nemeth E, Ganz T. The role of hepcidin in iron metabolism. Acta Haematol. 2009;122(2–3):78–86.
  9. Ganz T, Nemeth E. Iron Balance and the Role of Hepcidin in Chronic Kidney Disease. Semin Nephrol [Internet]. 2016;36(2):87–93.
  10. Gabay C, Lamacchia C, Palmer G. IL-1 pathways in inflammation and human diseases. Nat Rev Rheumatol. 2010;6(4):232–41.
  11. Boato F, Hechler D, Rosenberger K, Lüdecke D, Peters EM, Nitsch R, et al. Interleukin-1 beta and neurotrophin-3 synergistically promote neurite growth in vitro. J Neuroinflammation. 2011;8:1–10.
  12. Kim KS, Jung H, Shin IK, Choi B, Kim DH. Induction of Interleukin-1 Beta ( IL-1 b ) is a Critical Component of Lung Inflammation During Influenza A ( H1N1 ) Virus Infection. 2015;1112:1104–12.
  13. Franchi L, Eigenbrod T, Muñoz-Planillo R, Nuñez G. The inflammasome: A caspase-1-activation platform that regulates immune responses and disease pathogenesis. Nat Immunol. 2009;10(3):241–7.
  14. Pullamsetti SS, Seeger W, Savai R. Classical IL-6 signaling: a promising therapeutic target for pulmonary arterial hypertension. J Clin Invest. 2018;128(5):1720–3.
  15. Sonnweber T, Boehm A, Sahanic S, Pizzini A, Aichner M, Sonnweber B, et al. Persisting alterations of iron homeostasis in COVID ‑ 19 are associated with non ‑ resolving lung pathologies and poor patients ’ performance : a prospective observational cohort study. Respir Res [Internet]. 2020;1–9.
  16. Farid Y, Bowman NS, Lecat P. Biochemistry, hemoglobin synthesis. 2019;
  17. Giardina B. Hemoglobin: Multiple molecular interactions and multiple functions. An example of energy optimization and global molecular organization. Mol Aspects Med. 2021;101040.
  18. Galaris D, Barbouti A, Pantopoulos K. BBA - Molecular Cell Research Iron homeostasis and oxidative stress : An intimate relationship ☆. BBA - Mol Cell Res [Internet]. 2019;1866(12):118535.
  19. Drakesmith H, Prentice A. Viral infection and iron metabolism. 2008;6(july):541–52.
  20. Total Iron-binding Capacity Calculated from Serum Transferrin Concentration or Serum Iron Concentration and Unsaturated Iron-binding Capacity,. 2003;(1):175–8.
  21. Bowen RAR, Remaley AT. Interferences from blood collection tube components on clinical chemistry assays. Biochem medica. 2014;24(1):31–44.
  22. Strzelak K, Rybkowska N, Wiśniewska A, Koncki R. Photometric flow analysis system for biomedical investigations of iron/transferrin speciation in human serum. Anal Chim Acta. 2017;995:43–51.
  23. Shah M, Danish L, Khan NU, Zaman F, Ismail M, Hussain M, et al. Determination of mutations in iron regulating genes of beta thalassemia major patients of Khyber Pakhtunkhwa, Pakistan. Mol Genet Genomic Med. 2020;8(9):1–10.
  24. Chaudhry ZR, Rashid E, Rasheed S, Aslam H, Shakir S, Rasheed F. Correlation of hemoglobin with recovery time in COVID 19 infected patients. Prof Med J. 2021;28(12):1692–5.
  25. Lippi G, Mattiuzzi C. Hemoglobin value may be decreased in patients with severe coronavirus disease 2019. Hematol Transfus cell Ther. 2020;42:116–7.
  26. Fouad SH, Allam MF, Taha SI, Okba AA, Hosny A, Moneer M, et al. Comparison of hemoglobin level and neutrophil to lymphocyte ratio as prognostic markers in patients with COVID-19. J Int Med Res. 2021;49(7):03000605211030124.
  27. Chaudhry ZR, Rasheed S, Shakir S, Rashid E, Ansari M, Rasheed F. Corona virus lowers hemoglobin more in severe infection than mild COVID-19 infection. Prof Med J. 2021;28(08):1211–4.
  28. De Benoist B, Cogswell M, Egli I, McLean E. Worldwide prevalence of anaemia 1993-2005; WHO global database of anaemia. 2008;
  29. Wessling-Resnick M. Iron homeostasis and the inflammatory response. Annu Rev Nutr. 2010;30:105–22.
  30. Eskeland B, Baerheim A, Ulvik R, Hunskaar S. Influence of mild infections on iron status parameters in women of reproductive age. Scand J Prim Health Care. 2002;20(1):50–6.
  31. Leermakers PA, Remels AH V, Zonneveld MI, Rouschop KMA, Schols AMWJ, Gosker HR. Iron deficiency‐induced loss of skeletal muscle mitochondrial proteins and respiratory capacity; the role of mitophagy and secretion of mitochondria‐containing vesicles. FASEB J. 2020;34(5):6703–17.
  32. Alipour R, Hashemi SH, Mikaeili F. Serum iron level in patients with COVID-19: a case report study. Int J Res Med Sci. 2020;8(7):2658.
  33. Rivera S. Hepcidin as the central mediator of anemia of inflammation. University of California, Los Angeles; 2006.
  34. Kelly AU, McSorley ST, Patel P, Talwar D. Interpreting iron studies. Bmj. 2017;357.
  35. Lv Y, Chen L, Liang X, Liu X, Gao M, Wang Q, et al. Association between iron status and the risk of adverse outcomes in COVID-19. Clin Nutr [Internet]. 2021;40(5):3462–9.
  36. Rose-John S. Rose-John S Interleukin-6 signalling in health and disease. F1000Res. 2020;9. F1000Research. 2020;9.
  37. Xiang Z, Liu J, Shi D, Chen W, Li J, Yan R, et al. Glucocorticoids improve severe or critical COVID-19 by activating ACE2 and reducing IL-6 levels. Int J Biol Sci. 2020;16(13):2382.
  38. Alsagaff MY, Mulia EPB. Hypertension and COVID-19: Potential use of beta-blockers and a call for randomized evidence. Indian Heart J. 2021;73(6):757–9.
  39. Vazquez-Oliva G, Fernandez-Real JM, Zamora A, Vilaseca M, Badimon L. Lowering of blood pressure leads to decreased circulating interleukin-6 in hypertensive subjects. J Hum Hypertens. 2005;19(6):457–62.
  40. Chaolu H, Zhang X, Li X, Li D. Circulating cytokines and lymphocyte subsets in patients who have recovered from COVID-19. 2020;
  41. Nemeth E, Rivera S, Gabayan V, Keller C, Taudorf S, Pedersen BK, et al. IL-6 is the necessary and sufficient cytokine for the induction of hepcidin during inflammation. J Clin Invest. 2004;113(9):1271–6.
  42. Haurani FI. Hepcidin and the anemia of chronic disease. Vol. 36, Annals of Clinical & Laboratory Science. Assoc Clin Scientists; 2006. p. 3–6.
  43. Le Gac G, Férec C. The molecular genetics of haemochromatosis. Eur J Hum Genet. 2005;13(11):1172–85.
  44. Brissot P, Pietrangelo A, Adams PC, De Graaff B, McLaren CE, Loréal O. Haemochromatosis. Nat Rev Dis Prim. 2018;4(1):1–15.