Genetic Association of Angiotensin-converting enzyme 2 ACE-2 (rs2285666) Polymorphism with the Susceptibility of COVID-19 Disease in Iraqi Patients

http://.www.doi.org/10.26538/tjnpr/v7i2.7

Authors

  • Risala H. Allami Department of Medical and Molecular Biotechnology, College of Biotechnology, Al-Nahrain University, Iraq
  • Athraa H. Hassoon Department of Biology, College of Education for Pure Science (Ibn Al-Haitham), University of Baghdad, Iraq
  • Yasir M. Abdulateef Department of Microbiology - Medical College -Anbar University-Iraq
  • Ali A. Ghani Al Kunooze University College- Department of Medical Laboratory Techniques -Basrah, Iraq
  • Shahad Jamal Al-Falahi Pedodontics and Prevention Department, College of Dentistry, Al-Farahidi University

Abstract

Significant risks to human health are posed by the 2019 coronavirus illness (COVID-19). SARS coronavirus type 2 receptor, also known as the major enzyme in the renin-angiotensin system  (RAS), angiotensin-converting enzyme 2 (ACE-2), connects COVID-19 and RAS. This study was conducted with the intention of determining whether or not RAS gene polymorphisms and ACE-2 (G8790A) play a part in the process of predicting susceptibility to infection with COVID-19. In this study 127 participants, 67 of whom were deemed by a physician to be in a severe state of illness, and 60 of whom were categorized as "healthy controls" .The genetic study included an extraction of genomic DNA from blood samples of each covid 19 patients and healthy controls, then amplification the site of SNP (rs2285666) Within the ACE2 gene by using specific primers, sequencing PCR products, and genotyping to detect the role of the ACE-2 gene (rs2285666) in the incidence of COVID-19. ACE-2 (rs2285666) is statistically associated to COVID-19. The COVID-19 group had 65.67 %of individuals with the wild-type homozygous genotype (GG) and 20% in the control group, while the control group had 63.33% of individuals with the mutant genotype (AA). Consequently, the wild-type homozygous (GG) and allele (G) may be considered a risk factor (etiological fraction E. F) for COVID-19 in Iraqi patients, whereas the mutant homozygous (AA) and allele (A) may be considered a protective factor (preventive fraction). The findings of the present study reveal that carriers of the GG genotype of ACE2 (rs2285666) are substantially more susceptible to COVID-19.

References

Villaquirán Hurtado AF, Ramos OA, Jácome SJ, Meza MD. Actividad física y ejercicio en tiempos de COVID-19. Ces Medicina. 2020; 34:51-58.

Vaduganathan M, Vardeny O, Michel T, McMurray JJ, Pfeffer MA, Solomon SD. Renin–angiotensin–aldosterone

system inhibitors in patients with Covid-19. N Engl J Med. 2020; 382(17):1653-1659.

Wu J, Deng W, Li S, Yang X. Advances in research on ACE2 as a receptor for 2019-nCoV. Cell Mol Life Sci. 2021; 78(2):531-544.

Costa LB, Perez LG, Palmeira VA, Macedo e Cordeiro T, Ribeiro VT, Lanza K, Simoes e Silva AC. Insights on SARSCoV-2 molecular interactions with the renin-angiotensin system. Front Cell Dev Biol. 2020; 8:559841.

Hamming I, Timens W, Bulthuis ML, Lely AT, Navis GV, van Goor H. Tissue distribution of ACE2 protein, the functional receptor for SARS coronavirus. A first step in understanding SARS pathogenesis. J Pathol. 2004; 203(2):631-637.

Li W, Moore MJ, Vasilieva N, Sui J, Wong SK, Berne MA, Somasundaran M, Sullivan JL, Luzuriaga K, Greenough TC, Choe H. Angiotensin-converting enzyme 2 is a functional receptor for the SARS coronavirus. Nature. 2003; 426(6965):450-454.

Chaoxin J, Daili S, Yanxin H, Ruwei G, Chenlong W, Yaobin T. The influence of angiotensin-converting enzyme 2 gene polymorphisms on type 2 diabetes mellitus and coronary heart disease. Eur Rev Med Pharmacol Sci. 2013;17(19):2654-2659.

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; 5:227.

Firouzabadi N, Farshadfar P, Haghnegahdar M, AlaviShoushtari A, Ghanbarinejad V. Impact of ACE2 genetic variant on antidepressant efficacy of SSRIs. Acta Neuropsychiatr. 2022; 34(1):30-66.

Kim L, Garg S, O’Halloran A, Whitaker M, Pham H, Anderson EJ, Armistead I, Bennett NM, Billing L, ComoSabetti K, ill M. Risk factors for intensive care unit admission and in-hospital mortality among hospitalized adults identified through the US coronavirus disease 2019 (COVID-19)-associated hospitalization surveillance network (COVID-NET). Clin Infect Dis. 2021; 72(9):e206-214.

Gómez J, Albaiceta GM, García-Clemente M, López-Larrea C, Amado-Rodríguez L, Lopez-Alonso I, Hermida T, Enriquez AI, Herrero P, Melón S, Alvarez-Argüelles ME. Angiotensin-converting enzymes (ACE, ACE2) gene variants and COVID-19 outcome. Gene. 2020; 762:145102.

Killerby ME, Link-Gelles R, Haight SC, Schrodt CA, England L, Gomes DJ, Shamout M, Pettrone K, O'Laughlin K, Kimball A, Blau EF. Characteristics associated with hospitalization among patients with COVID-19—Metropolitan Atlanta, Georgia, March–April 2020. Morb Mortal Wkly. 2020; 69(25):790-794.

Klein SL, Dhakal S, Ursin RL, Deshpande S, Sandberg K, Mauvais-Jarvis F. Biological sex impacts COVID-19 outcomes. PLoS pathogens. 2020; 16(6):e1008570.

Liu YC, Kuo RL,Shih SR. COVID-19: The first documented coronavirus pandemic in history. Biomed j. 2020; 43(4):328-333.

Liu Y, Yang Y, Zhang C, Huang F, Wang F, Yuan J, Wang Z, Li J, Li J, Feng C, Zhang Z. Clinical and biochemical indexes from 2019-nCoV infected patients linked to viral loads and lung injury. Sci China Life Sci. 2020; 63(3):364-374.

Holt A, Mizrak I, Lamberts M, Madsen PL. Influence of inhibitors of the renin–angiotensin system on risk of acute respiratory distress syndrome in Danish hospitalized COVID-19 patients. J Hypertens; 2020; 38(8): 1612-1613.

Zhou C, Chen Y, Ji Y, He X, Xue, D. Increased serum levels of hepcidin and ferritin are associated with severity of COVID-19. Med Sci Monit, 2020; 26: e926178.

Singh A. , Gupta R, Ghosh A, & Misra, A. Diabetes in COVID-19: Prevalence, pathophysiology, prognosis and practical considerations. Diabetes & Metabolic Syndrome: Clin. Res. 2020; 14(4), 303-310.

Yang J, Zheng Y, Gou X, Pu K, Chen Z, Guo, Q, Zhou, Y. Prevalence of comorbidities in the novel Wuhan coronavirus (COVID-19) infection: a systematic review and metaanalysis. Int J Infect Dis, 2020; 10 (10.1016).

Srivastava A, Bandopadhyay A, Das D, Pandey RK, Singh V, Khanam N, Srivastava N, Singh PP, Dubey PK, Pathak A, Gupta P. Genetic association of ACE2 rs2285666 polymorphism with COVID-19 spatial distribution in India. Front Neurol. 2020; 11:1163.

Möhlendick B, Schönfelder K, Breuckmann K, Elsner C, Babel N, Balfanz P, Dahl E, Dreher M, Fistera D, Herbstreit F, Hölzer B. ACE2 polymorphism and susceptibility for SARS-CoV-2 infection and severity of COVID-19. Pharmacogenet. Genomics. 2021;31(8):165-171.

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(1):1-9.

Ferreira AJ, Murça TM, Fraga-Silva RA, Castro CH, Raizada MK, Santos RA. New cardiovascular and pulmonary therapeutic strategies based on the Angiotensin-converting enzyme 2/angiotensin-(1–7)/mas receptor axis. Int J Hypertens 2012; 2012:5.

Tan WS, Liao W, Zhou S, Mei D, Wong WS. Targeting the renin–angiotensin system as novel therapeutic strategy for pulmonary diseases. Curr Opin Pharmacol. 2018; 40:9–17.

Srivastava P, Badhwar S, Chandran DS, Jaryal AK, Jyotsna VP, Deepak KK. Imbalance between Angiotensin IIAngiotensin (1-7) systems is associated with vascular endothelial dysfunction and inflammation in type 2 diabetes with newly diagnosed hypertension. Diabetes & Metabolic Syndrome: Clin Res. 2019; 13(3):2061-2068.

Cook JR, Ausiello J. Functional ACE2 deficiency leading to angiotensin imbalance in the pathophysiology of COVID-19. Rev Endocr Metab Disord. 2022; 23(2):151-70.

Lanza K, Perez LG, Costa LB, Cordeiro TM, Palmeira VA, Ribeiro VT, Simoes e Silva AC. Covid-19: the renin–angiotensin system imbalance hypothesis. Clin sci. 2020; 134(11):1259-1264.

Gemmati D, Tisato V. Genetic hypothesis and pharmacogenetics side of renin-angiotensin-system in COVID-19. Genes. 2020; 11(9):1044.

Alimoradi N, Firouzabadi N. Impact of Genetics on Predisposition and Prognosis of COVID-19. Trends Pharmacol Sci. 2021; 7(2):73-80.

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.

Abdul-Gani MN, Laftaah BA. Purification and characterization of chondroitinase ABC from Proteus vulgaris, an Iraqi clinically isolate. Curr Sci. 2017:2134-2140.

Kadhim AL-Imam MJ, AL-Rubaii BA. The influence of some amino acids, vitamins and anti-inflammatory drugs on activity of chondroitinase produced by Proteus vulgaris caused urinary tract infection. Iraqi J Sci., 2016; 57 (4A):2412-2421.

Hashim ST, Fakhry SS, Rasoul LM, Saleh TH, Alrubaii BA. Genotyping toxins of Clostridium perfringens strains of rabbit and other animal origins. Trop J Nat Prod Res. 2021; 5(4):613-616.

Fakhry SS, Hammed ZN, Bakir WA-E, ALRubaii BAL. Identification of methicillin-resistant strains of Staphylococcus aureus isolated from humans and food sources by use mecA 1 and mecA 2 genes in Pulsed-field gel electrophoresis technique. Bionatura. 2022;7(2):44. doi: 10.21931/RB/2022.07.02.44.

Ali M, Al-Rubaii B. Study of the Effects of Audible Sounds and Magnetic Fields on Staphylococcus aureus Methicillin

Resistance and mecA Gene Expression. Trop J Nat Prod Res. 2021; 5(5):825-830.

Abdulrazaq, R.A., Mahmood, W.S., Alwan, B., Saleh, T.H., Hashim, S.T., Al-Rubaii, B.A.L. Biological Study of protease produced by clinical isolates of Staphylococcus aureus. Res J Pharm Technol.2022; 15(12):5415-5420.

Abdulkaliq Awadh H, Hammed ZN, Hamzah SS, Saleh TH, AL-Rubaii BA. Molecular identification of intracellular survival related Brucella melitensis virulence factors. Biomedicine. 2022; 42(4):761-765.

Al-Rubii, B.A.L. Cloning LasB gene of Pseudomonas aeruginosa eiastase 10104-2aI in E. coli BL21 and E.coliDH5α and investigated their effect on the stripping of Vero cells. Pakistan J Biotechnol. 2017; 14(4):697-705.

Abdulla L, Ismael MK, Salih TA, Malik SN, Al-Rubaii BA. Genotyping and evaluation of interleukin-10 and soluble HLA-G in abortion due to toxoplasmosis and HSV-2 infections. Ann Parasitol., 68(2):385–390.

Jiad AL, Ismael MK, Muhsin SS, Al-Rubaii BA. ND2 Gene Sequencing of Sub fertile Patients Recovered from COVID-19 in Association with Toxoplasmosis. Bionatura. 2022; 7(3):1-4.

Rasoul, L.M., Marhoon, A.A., Albaayit, S.F.A., Ali, R.W., Saleh, T.H., Al-Rubaii, B.A.L. Cytotoxic effect of cloned EGFP gene on NCI-H727 cell line via genetically engineered gene transfer system. Biomedicine. 2022; 42(5):938-942.

Rasoul LM, Nsaif MM, Al-Tameemi MT, Al-Rubaii BA. Estimation of primer efficiency in multiplex PCR for detecting SARS-Cov-2 variants. Bionatura, 2022; 7(3):48.

Ahmed AA, Khaleel KJ, Fadhel AA, Al-Rubaii BA. Chronic Myeloid Leukemia: A retrospective study of clinical and pathological features. Bionatura. 2022; 7(3):41.

Ali SM, Lafta BA, Al-Shammary AM, Salih HS. In vivooncolytic activity of non-virulent newcastle disease virus Iraqi strain against mouse mammary adenocarcinoma. In AIP Conference Proceedings 2021; 2372 (1):030010.

Ali SM, Laftah BA, Al-Shammary AM, Salih HS. Study the role of bacterial neuraminidase against adenocarcinoma cells in vivo. In AIP Conference Proceedings 2021; 2372(1): 030009.

Salih HS, Al-Shammari AM, Laftaah BA. Intratumoral coadministration of oncolytic newcastle disease virus and bacterial hyaluronidase enhances virus potency in tumor models. J Glob Pharma Technol. 2018; 10(10):303-10.

Ahmed AW, Ahmed RN, Naif MM, Yahya MT, Maulood KS, Alchalabi GB, Mohammed AG. Chest CT findings and experience in 100 COVID19 patients in Mosul city, Iraq. Biomedicine. 2021 Dec 31; 41(4):793-798.

Suhail H, Abdulrahman D, Ahmed A. Fetal Biometry and Doppler Assessment of Pregnant Women with COVID-19. Int J Biomed. 2022; 12(4):554-559.

Published

2023-02-28

How to Cite

Allami, R. H., Hassoon, A. H., Abdulateef, Y. M., Ghani, A. A., & Al-Falahi, S. J. (2023). Genetic Association of Angiotensin-converting enzyme 2 ACE-2 (rs2285666) Polymorphism with the Susceptibility of COVID-19 Disease in Iraqi Patients: http://.www.doi.org/10.26538/tjnpr/v7i2.7. Tropical Journal of Natural Product Research (TJNPR), 7(2), 2346–2351. Retrieved from https://tjnpr.org/index.php/home/article/view/1625