ACE II RECEPTOR GENE POLYMORPHISM, QUANTITATIVE IMMUNOLOGICAL DETECTION OF ACE II RECEPTORS AND MICRONUTRIENTS ASSOCIATION WITH HOSPITAL ACQUIRED COVID-19 PATIENTS
Main Article Content
Keywords
COVID-19, ACE2, Vitamin D, Immunocompromised, Vitamin B12
Abstract
The outburst of the immensely communicable COVID-19 has proposed a consequential challenge to the world’s health, particularly for those who are already countering any disease and are thus immunocompromised. COVID-19 uses human ACE2 (angiotensin-converting enzyme 2), an epithelial cell of the lungs with receptors, to gain entry into human cells, which is the first step of viral infection. In this study, we have evaluated the levels of ACE2 in serum and its gene expression to confirm that high ACE2 levels and its gene polymorphism could be risk factors for COVID-19, or those patients, who were COVID-positive and immunocompromised, have more ACE2 levels in comparison to non-COVID-patients with same population. Secondly, we assessed the levels of micronutrients, which showed the risk factors for COVID-19. Our data revealed that the gene expression of the ACE2 enzyme and its genotype G8790A polymorphism are associated with the progression of the disease. The levels of micronutrients were also found to be linked with COVID-19 progression in immunocompromised patients. The findings of the study have suggested that if levels of ACE2 enzyme and micronutrients are controlled, then the progression of the disease can be decreased
References
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31. Al Faraj S, Al Mutairi K. Vitamin D deficiency and chronic low back pain in Saudi Arabia. Spine . 2003;28: 177–179.
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2. Wu Z, McGoogan JM. 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: 1239–1242.
3. Banerjee A, Kulcsar K, Misra V, Frieman M, Mossman K. Bats and coronaviruses. Viruses. 2019; 11 (1): 41. 2019.
4. Imai Y, Kuba K, Penninger JM. The discovery of angiotensin-converting enzyme 2 and its role in acute lung injury in mice. Exp Physiol. 2008;93: 543–548.
5. Chi Y, Ge Y, Wu B, Zhang W, Wu T, Wen T, et al. Serum Cytokine and Chemokine Profile in Relation to the Severity of Coronavirus Disease 2019 in China. J Infect Dis. 2020;222: 746–754.
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7. Cao Y, Li L, Feng Z, Wan S, Huang P, Sun X, et al. Comparative genetic analysis of the novel coronavirus (2019-nCoV/SARS-CoV-2) receptor ACE2 in different populations. Cell Discov. 2020;6: 11.
8. Kuba K, Imai Y, Ohto-Nakanishi T, Penninger JM. Trilogy of ACE2: A peptidase in the renin–angiotensin system, a SARS receptor, and a partner for amino acid transporters. PharmacolTher. 2010;128: 119–128.
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10. Harmer D, Gilbert M, Borman R, Clark KL. Quantitative mRNA expression profiling of ACE 2, a novel homologue of angiotensin converting enzyme. FEBS Lett. 2002;532: 107–110.
11. Velkoska E, Patel SK, Burrell LM. Angiotensin converting enzyme 2 and diminazene: role in cardiovascular and blood pressure regulation. CurrOpinNephrolHypertens. 2016;25: 384–395.
12. Luo Y, Liu C, Guan T, Li Y, Lai Y, Li F, et al. Association of ACE2 genetic polymorphisms with hypertension-related target organ damages in south Xinjiang. Hypertens Res. 2019;42: 681–689.
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14. Barash A, Machluf Y, Ariel I, Dekel Y. The Pursuit of COVID-19 Biomarkers: Putting the Spotlight on ACE2 and TMPRSS2 Regulatory Sequences. Front Med. 2020;7: 582793.
15. Alimoradi N, Firouzabadi N. impact of genetics on predisposition and prognosis of COVID-19. Trends in Pharmaceutical Sciences. 2021;7. Available: https://journals.sums.ac.ir/article_47482_ea202aa2ea8b29f2944eed3e2d3d45c6.pdf
16. Gemmati D, Tisato V. Genetic Hypothesis and Pharmacogenetics Side of Renin-Angiotensin-System in COVID-19. Genes . 2020;11. doi:10.3390/genes11091044
17. Çelik SK, Genç GÇ, Piskin N, Acikgoz B, Altınsoy B, İşsiz BK, et al. ACE I/D and ACE2 receptor gene (RS2106809, RS2285666) polymorphisms is not related to the clinical course of COVID-19; a case study. Authorea Preprints. 2021. Available: https://www.authorea.com/doi/full/10.22541/au.161572992.20220722
18. Srivastava A, Bandopadhyay A, Das D, Pandey RK, Singh V, Khanam N, et al. Genetic Association of ACE2 rs2285666 Polymorphism With COVID-19 Spatial Distribution in India. Front Genet. 2020;11: 564741.
19. Patel SK, Velkoska E, Freeman M, Wai B, Lancefield TF, Burrell LM. From gene to protein—experimental and clinical studies of ACE2 in blood pressure control and arterial hypertension. Front Physiol. 2014;5. doi:10.3389/fphys.2014.00227
20. Calcagnile M, Forgez P, Iannelli A, Bucci C, Alifano M, Alifano P. Molecular docking simulation reveals ACE2 polymorphisms that may increase the affinity of ACE2 with the SARS-CoV-2 Spike protein. Biochimie. 2021;180: 143–148.
21. Ashoor D, Ben Khalaf N, Marzouq M. A computational approach to evaluate the combined effect of SARS-CoV-2 RBD mutations and ACE2 receptor genetic variants on infectivity: The COVID-19 …. Frontiers in cellular. 2021. Available: https://www.frontiersin.org/articles/10.3389/fcimb.2021.707194/pdf
22. Pouladi N, Abdolahi S. Investigating the ACE2 polymorphisms in COVID-19 susceptibility: An in silico analysis. Molecular Genetics & Genomic Medicine. 2021;9: e1672.
23. Firouzabadi N, Shafiei M, Bahramali E, Ebrahimi SA, Bakhshandeh H, Tajik N. Association of angiotensin-converting enzyme (ACE) gene polymorphism with elevated serum ACE activity and major depression in an Iranian population. Psychiatry Res. 2012;200: 336–342.
24. Firouzabadi N, Tajik N, Shafiei M, Ebrahimi SA, Bakhshandeh H. Interaction of A-240T and A2350G related genotypes of angiotensin-converting enzyme (ACE) is associated with decreased serum ACE activity and blood pressure in a healthy Iranian population. Eur J Pharmacol. 2011;668: 241–247.
25. Zhu X, Bouzekri N, Southam L, Cooper RS, Adeyemo A, McKenzie CA, et al. Linkage and Association Analysis of Angiotensin I–Converting Enzyme (ACE)–Gene Polymorphisms with ACE Concentration and Blood Pressure. Am J Hum Genet. 2001;68: 1139–1148.
26. Hoffmann M, Kleine-Weber H, Schroeder S, Krüger N, Herrler T, Erichsen S, et al. SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor. Cell. 2020;181: 271–280.e8.
27. Voors AA, Pinto YM, Buikema H, Urata H, Oosterga M, Rooks G, et al. Dual pathway for angiotensin II formation in human internal mammary arteries. Br J Pharmacol. 1998;125: 1028–1032.
28. Uhal BD, Kyong Kim J, Li X, Molina-Molina M. Angiotensin-TGF-1 Crosstalk in Human Idiopathic Pulmonary Fibrosis:Autocrine Mechanisms in Myofibroblasts and Macrophages. Curr Pharm Des. 2007;13: 1247–1256.
29. Visser M, Deeg DJH, Lips P, Longitudinal Aging Study Amsterdam. Low vitamin D and high parathyroid hormone levels as determinants of loss of muscle strength and muscle mass (sarcopenia): the Longitudinal Aging Study Amsterdam. J ClinEndocrinolMetab. 2003;88: 5766–5772.
30. Diamond TH, Levy S, Smith A, Day P. High bone turnover in Muslim women with vitamin D deficiency. Med J Aust. 2002;177: 139–141.
31. Al Faraj S, Al Mutairi K. Vitamin D deficiency and chronic low back pain in Saudi Arabia. Spine . 2003;28: 177–179.
32. Vitamin D. deficiency. Holick MF. N Engl J Med. 2007;357: 266–281.
33. Zhang M, Han W, Hu S, Xu H. Methylcobalamin: a potential vitamin of pain killer. Neural Plast. 2013;2013: 424651.
34. Andres E, Dali-Youcef N. Chapter 19 - Cobalamin (vitamin B12) malabsorption. In: Patel VB, editor. Molecular Nutrition. Academic Press; 2020. pp. 367–386.
35. Herrmann W, Obeid R. Causes and early diagnosis of vitamin B12 deficiency. DeutschesÄrzteblatt International. 2008;105: 680.
36. Maggini S, Pierre A, Calder PC. Immune Function and Micronutrient Requirements Change over the Life Course. Nutrients. 2018;10. doi:10.3390/nu10101531
37. Yi L, Gu YH, Wang XL, An LZ, Xie XD, Shao W, et al. Association of ACE, ACE2 and UTS2 polymorphisms with essential hypertension in Han and Dongxiang populations from north-western China. J Int Med Res. 2006;34: 272–283.
38. Ni W, Yang X, Yang D, Bao J, Li R, Xiao Y, et al. Role of angiotensin-converting enzyme 2 (ACE2) in COVID-19. Crit Care. 2020;24: 422.
39. Oudit GY, Kassiri Z, Jiang C, Liu PP, Poutanen SM, Penninger JM, et al. SARS-coronavirus modulation of myocardial ACE2 expression and inflammation in patients with SARS. Eur J Clin Invest. 2009;39: 618–625.
40. Getachew B, Tizabi Y. Vitamin D and COVID-19: Role of ACE2, age, gender, and ethnicity. J Med Virol. 2021;93: 5285–5294.
41. Chaudhry F, Lavandero S, Xie X, Sabharwal B, Zheng Y-Y, Correa A, et al. Manipulation of ACE2 expression in COVID-19. Open Heart. 2020;7. doi:10.1136/openhrt-2020-001424
42. Li G, He X, Zhang L, Ran Q, Wang J, Xiong A, et al. Assessing ACE2 expression patterns in lung tissues in the pathogenesis of COVID-19. J Autoimmun. 2020;112: 102463.
43. Gagliardi MC, Tieri P, Ortona E, Ruggieri A. ACE2 expression and sex disparity in COVID-19. Cell Death Discov. 2020;6: 37.
44. Fan C, Lu W, Li K, Ding Y, Wang J. ACE2 Expression in Kidney and Testis May Cause Kidney and Testis Infection in COVID-19 Patients. Front Med. 2020;7: 563893.
45. Pinto BGG, Oliveira AER, Singh Y, Jimenez L, Gonçalves ANA, Ogava RLT, et al. ACE2 Expression is Increased in the Lungs of Patients with Comorbidities Associated with Severe COVID-19. medRxiv. 2020. doi:10.1101/2020.03.21.20040261
46. Higham A, Singh D. Increased ACE2 Expression in Bronchial Epithelium of COPD Patients who are Overweight. Obesity . 2020;28: 1586–1589.
47. Tavares C de AM, Avelino-Silva TJ, Benard G, Cardozo FAM, Fernandes JR, Girardi ACC, et al. ACE2 Expression and Risk Factors for COVID-19 Severity in Patients with Advanced Age. Arq Bras Cardiol. 2020;115: 701–707.
48. Patel AB, Verma A. Nasal ACE2 Levels and COVID-19 in Children. JAMA: the journal of the American Medical Association. jamanetwork.com; 2020. pp. 2386–2387.
49. Chen L, Li X, Chen M, Feng Y, Xiong C. The ACE2 expression in human heart indicates new potential mechanism of heart injury among patients infected with SARS-CoV-2. Cardiovasc Res. 2020;116: 1097–1100.
50. Verdecchia P, Cavallini C, Spanevello A, Angeli F. The pivotal link between ACE2 deficiency and SARS-CoV-2 infection. Eur J Intern Med. 2020;76: 14–20.
51. Wysocki J, Ye M, Soler MJ, Gurley SB, Xiao HD, Bernstein KE, et al. ACE and ACE2 activity in diabetic mice. Diabetes. 2006;55: 2132–2139.
52. Wu Y-H, Li J-Y, Wang C, Zhang L-M, Qiao H. The ACE2 G8790A Polymorphism: Involvement in Type 2 Diabetes Mellitus Combined with Cerebral Stroke. J Clin Lab Anal. 2017;31. doi:10.1002/jcla.22033
53. Wang Z, Yuan Z, Matsumoto M, Hengge UR, Chang Y-F. Immune responses with DNA vaccines encoded different gene fragments of severe acute respiratory syndrome coronavirus in BALB/c mice. BiochemBiophys Res Commun. 2005;327: 130–135.
54. Möhlendick B, Schönfelder K, Breuckmann K, Elsner C, Babel N, Balfanz P, et al. ACE2 polymorphism and susceptibility for SARS-CoV-2 infection and severity of COVID-19. Pharmacogenet Genomics. 2021. Available: https://www.ncbi.nlm.nih.gov/pmc/articles/pmc8415730/
55. Alimoradi N, Sharqi M, Firouzabadi D, Sadeghi MM, Moezzi MI, Firouzabadi N. SNPs of ACE1 (rs4343) and ACE2 (rs2285666) genes are linked to SARS-CoV-2 infection but not with the severity of disease. Virol J. 2022;19: 48.
56. Chen N, Zhou M, Dong X, Qu J, Gong F, Han Y, et al. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. Lancet. 2020;395: 507–513.
57. Vardavas CI, Nikitara K. COVID-19 and smoking: A systematic review of the evidence. TobInduc Dis. 2020;18: 20.
58. Ghosh S, Klein RS. Sex Drives Dimorphic Immune Responses to Viral Infections. J Immunol. 2017;198: 1782–1790.
59. Prelack K, Sheridan RL. Micronutrient supplementation in the critically ill patient: strategies for clinical practice. J Trauma. 2001;51: 601–620.
60. Fletcher RH, Fairfield KM. Vitamins for chronic disease prevention in adults: clinical applications. JAMA. 2002;287: 3127–3129.
61. Fairfield KM, Fletcher RH. Vitamins for chronic disease prevention in adults: scientific review. JAMA. 2002;287: 3116–3126.
62. National Research Council, Division on Earth and Life Studies, Commission on Life Sciences, Committee on Diet and Health. Diet and Health: Implications for Reducing Chronic Disease Risk. National Academies Press; 1989.
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Dec 11, 2023
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How to Cite
Amber Khan, Saira Yahya, Anum Siraj, Maliaka Arif, Muhammad Umair, Muhammad Saleem Iqbal Khan, Muhammad Abubakar, Rooma Ayyoub, & Saleem Awan. (2023). ACE II RECEPTOR GENE POLYMORPHISM, QUANTITATIVE IMMUNOLOGICAL DETECTION OF ACE II RECEPTORS AND MICRONUTRIENTS ASSOCIATION WITH HOSPITAL ACQUIRED COVID-19 PATIENTS. Journal of Population Therapeutics and Clinical Pharmacology, 30(19), 391-402. https://doi.org/10.53555/jptcp.v30i19.3672
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Author Biographies
Amber Khan
Biosciences Department, Shaheed Zulfikar Ali Bhutto Institute of Science and Technology (SZABIST) Karachi
Saira Yahya
Associate Professor, Biosciences Department, Shaheed Zulfikar Ali Bhutto Institute of Science and Technology (SZABIST) Karachi
Anum Siraj
Biosciences Department, Shaheed Zulfikar Ali Bhutto Institute of Science and Technology (SZABIST) Karachi
Maliaka Arif
MBBS. Dow International Medical College, Karachi
Muhammad Umair
Center of Excellence in Molecular Biology, University of the Punjab
Muhammad Saleem Iqbal Khan
Department of Physiology and Department of Cardiology of the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
Muhammad Abubakar
Cancer Genetics and Epigenetic Lab, Biosciences Department, COMSATS University Islamabad,
Rooma Ayyoub
Cancer Genetics and Epigenetic Lab, Biosciences Department, COMSATS University Islamabad
Saleem Awan
Biosciences Department, Shaheed Zulfikar Ali Bhutto Institute of Science and Technology (SZABIST) Karachi
How to Cite
Amber Khan, Saira Yahya, Anum Siraj, Maliaka Arif, Muhammad Umair, Muhammad Saleem Iqbal Khan, Muhammad Abubakar, Rooma Ayyoub, & Saleem Awan. (2023). ACE II RECEPTOR GENE POLYMORPHISM, QUANTITATIVE IMMUNOLOGICAL DETECTION OF ACE II RECEPTORS AND MICRONUTRIENTS ASSOCIATION WITH HOSPITAL ACQUIRED COVID-19 PATIENTS. Journal of Population Therapeutics and Clinical Pharmacology, 30(19), 391-402. https://doi.org/10.53555/jptcp.v30i19.3672