Distribution of ACE gene I/D genotypes and clinical characteristics of patients with hypertension and COVID-19 in Indonesia

Main Article Content

Ingrid Faustine https://orcid.org/0000-0001-6700-4514
Deli Marteka https://orcid.org/0000-0003-0687-2670
Lisa Amelia
Shellinna Kurniawati
Amarila Malik https://orcid.org/0000-0003-4899-6778
Retnosari Andrajati https://orcid.org/0000-0003-1319-1240
Septelia Inawati Wanandi https://orcid.org/0000-0002-7963-8853
Eko Supriyanto https://orcid.org/0000-0002-6766-793X

Keywords

hypertension, COVID-19, ACE gene, insertion-deletion, SARS-CoV-2

Abstract

Background: Suppression of the renin-angiotensin system by SARS-CoV-2 binding changes the balance between ACE and ACE2, which affects blood pressure regulation. The ACE gene polymorphisms in intron 16 are associated with susceptibility to SARS-CoV-2 infection in patients with hypertension. Objective: This study analyzed the ACE gene polymorphism distribution and determined the probability of infection and severity of hypertension in COVID-19 patients. Methods: One hundred and six adult subjects were involved in this cross-sectional study, comprising 95 COVID-19 subjects and 91 non-COVID-19 subjects from two parts of Indonesia in 2021, i.e. Palu City, Central Celebes, and Lahat District, South Sumatra, DNAs extracted from whole blood were analyzed for I/D polymorphisms by Polymerase Chain Reaction (PCR) method. Results: Distribution of ACE genotypes were found as follows; II (53%), ID (38%), and DD (9%). The percentage of hypertension and the severity of COVID-19 in the Palu population were higher than those in Lahat District, i.e., 44% vs. 14% and 80% vs. 46%, respectively. Although there was no significant association between the I/D genotypes and susceptibility or severity of COVID-19 (p> 0.05), it appeared that subjects with hypertension and dyspnea symptoms were five times more susceptible to a moderate-severe symptom that required hospitalization and was associated with a fivefold increase in the risk of dyspnea symptoms that required hospitalization. However, comorbid hypertension was associated with moderate to severe COVID-19 (p=0.007). Conclusion: It can be assumed that in our studied population, ACE gene I/D polymorphisms and hypertension are not associated with susceptibility to SARS-CoV-2 infection, but the presence of comorbid hypertension is a risk factor for more severe COVID-19.

Abstract 181 | PDF Downloads 41

References

1. WHO Coronavirus (COVID-19) Dashboard | WHO Coronavirus (COVID-19) Dashboard With Vaccination Data. Available at: https://covid19.who.int/ (Accessed: 22 Nov 2022).
2. Fei Zhou et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet. 2020;395(March):1053-62. https://doi.org/10.1016/S0140-6736(20)30566-3
3. Voss JD, Skarzynski M, McAuley EM, et al. Variants in SARS-CoV-2 associated with mild or severe outcome. Evol Med Public Heal. 2021;9(1):267-75. https://doi.org/10.1093/emph/eoab019
4. Harapan H, Itoh N, Yufika A, et al. Coronavirus disease 2019 (COVID-19): A literature review. J Infect Public Health. 2020;13(5):667-73. https://doi.org/10.1016/j.jiph.2020.03.019
5. Karyono DR, Wicaksana AL. Current prevalence, characteristics, and comorbidities of patients with COVID-19 in Indonesia. J Community Empower Heal. 2020;3(2):77. https://doi.org/10.22146/jcoemph.57325
6. Kamyshnyi A, Krynytska I, Matskevych V, et al. Arterial hypertension as a risk comorbidity associated with covid-19 pathology. Int J Hypertens. 2020;2020. https://doi.org/10.1155/2020/8019360
7. Tim Riskesdas 2018. Laporan nasional RISKESDAS 2018 [Internet]. Lembaga Penelitian dan Pengembangan Kesehatan; 2019. 155-57 p. Available at: http://labdata.litbang.kemkes.go.id/images/download/laporan/RKD/2018/Laporan_Nasional_ RKD2018_FINAL.pdf
8. Faustine I, Malik A, Andrajati R, Wanandi SI. Clinical Characteristics and Severity Profile of COVID-19 Patient with Hypertension in Palu, Central Sulawesi. Indones J Pharm. 2021;32(4):563-72. https://doi.org/10.22146/ijp.2729
9. Marteka D, Malik A, Faustine I, Syafhan NF. Clinical profile , treatment , and outcomes of patients with COVID-19 in a tertiary referral hospital in South Sumatera , Indonesia : A retrospective single-center study. Belitung Nurs J. 2022;8(6):529-37. https:// doi.org/10.33546/bnj.2302
10. Peta Sebaran | Covid19.go.id [Internet]. Available at: https://covid19.go.id/peta-sebaran. (Accessed: 22 Nov 2022).
11. Wong MKS. Angiotensin converting enzymes. In: Handbook of hormones comparative endocrinology for basic and clinical Research. 2016. p. 263-5. https://doi.org/10.1016/B978-0-12-801028-0.00254-3
12. M. Al-Kuraishy H, S. Al-Niemi M, R. Hussain N, et al. The Potential Role of Renin Angiotensin System (RAS) and Dipeptidyl Peptidase-4 (DPP-4) in COVID-19: Navigating the Uncharted. In: Selected Chapters from the Renin-Angiotensin System. IntechOpen; 2020. https://doi.org/10.5772/intechopen.92837
13. Gheblawi M, Wang K, Viveiros A,et al. Angiotensin-Converting Enzyme 2: SARS-CoV-2 Receptor and Regulator of the Renin- Angiotensin System: Celebrating the 20th Anniversary of the Discovery of ACE2. Circ Res. 2020;126:1456-74. https://doi. org/10.1161/CIRCRESAHA.120.317015
14. Sieńko J, Kotowski M, Bogacz A, et al. COVID-19: The influence of ACE genotype and ACE-I and ARBs on the course of SARSCoV- 2 infection in elderly patients. Clin Interv Aging. 2020;15:1231-40. https://doi.org/10.2147/CIA.S261516
15. Jin Y, Yang H, Ji W, et al. Virology, epidemiology, pathogenesis, and control of covid-19. Viruses. 2020;12(4):1-17. https://doi. org/10.3390/v12040372
16. Oliveira-Paula GH, Pereira SC, Tanus-Santos JE, et al. Pharmacogenomics and hypertension: Current insights. Pharmgenomics Pers Med. 2019;12:341-59. https://doi.org/10.2147/PGPM.S230201
17. He Q, Fan C, Yu M, et al. Associations of ACE Gene Insertion / Deletion Polymorphism , ACE Activity , and ACE mRNA Expression with Hypertension in a Chinese Population. PLoS One. 2013;8(10):1-9. https://doi.org/10.1371/journal.pone.0075870
18. Faustine I, Marteka D, Malik A, Supriyanto E, Syafhan NF. Genotype variation of ACE and ACE2 genes affects the severity of COVID-19 patients. BMC Res Notes. 2023;16(1):1-6. https://doi.org/10.1186/s13104-023-06483-z
19. Chung CM, Wang RY, Fann CSJ, et al. Fine-Mapping Angiotensin-Converting Enzyme Gene: Separate QTLs Identified for Hypertension and for ACE Activity. PLoS One. 2013;8(3):e56119. https://doi.org/10.1371/journal.pone.0056119
20. Gómez J, Albaiceta GM, García-clemente M, et al. Angiotensin-converting enzymes (ACE, ACE2) gene variants and COVID-19 outcome. Gene J. 2020;762(January):145102. https://doi.org/10.1016/j.gene.2020.145102
21. Health NI of. Coronavirus Disease 2019 (COVID-19) Treatment Guidelines. 2019;130. 
22. Mancia G, De Backer G, Dominiczak A, et al. 2018 ESC/ESH Guidelines for the management of arterial hypertension: The Task Force for the Management of Arterial Hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC). Vol. 25, Journal of Hypertension. 2018. 3021-3104 p. https://doi.org/10.1097/HJH.0b013e3281fc975a
23. Garabed Eknoyan M, Norbert Lameire, MD P. KDIGO 2012 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease. Vol. 3, Kidney International supplements. 2013. https://doi.org/10.3182/20140824-6-za-1003.01333
24. Body mass index - BMI. Available at: https://www.euro.who.int/en/health-topics/disease-prevention/nutrition/a-healthylifestyle/ body-mass-index-bmi. (Accessed: 13 Mar 2022)
25. Mafra FFP, Gattai PP, Macedo MM, et al. The angiotensin-I-converting enzyme insertion/deletion in polymorphic element codes for an AluYa5 RNA that downregulates gene expression. Pharmacogenomics J. 2018;18(4):517-27. https://doi.org/10.1038/ s41397-018-0020-x
26. A. Syed S. ACE I/D Polymorphism in Hypertensive Patients of Kashmiri Population. Cardiol Res. 2010;1(1):1-7. https://doi. org/10.4021/cr101e
27. Hubacek JA, Ladislav Dusek, Ondrej Majek, et al. ACE I/D polymorphism in Czech first-wave SARS-CoV-2-positive survivors. Clin Chim Acta. 2021;519(January):206-9. https://doi.org/10.1016/j.cca.2021.04.024
28. Jacobs M, Lahousse L, Van Eeckhoutte HP, et al. Effect of ACE1 polymorphism rs1799752 on protein levels of ACE2, the SARSCoV- 2 entry receptor, in alveolar lung epithelium. ERJ Open Res. 2021;7(2):1-4. https://doi.org/10.1183/23120541.00940- 2020
29. Faustine I, Malik A, Andrajati R, Wanandi SI. Detection of ACE Gene SNPs Using rhAmp Genotyping Platform and Their Association with I/D Polymorphism in COVID-19 Patients with Hypertension. Indones J Pharm. 2023;34(4):640-50. https://doi. org/10.22146/ijp.5647
30. Han C, Han X, Liu F, et al. Ethnic differences in the association between angiotensin‐converting enzyme gene insertion/ deletion polymorphism and peripheral vascular disease: A meta‐analysis. Chronic Dis Transl Med. 2017;3(4):230-41. https:// doi.org/10.1016/j.cdtm.2017.07.002
31. Zeng W li, Yang S kun, Song N, et al. The impact of angiotensin converting enzyme insertion/deletion gene polymorphism on diabetic kidney disease: A debatable issue. Nefrología. 2021;933(x x):17. https://doi.org/10.1016/j.nefro.2021.07.008
32. Heidari F, Vasudevan R, Mohd Ali SZ, et al. Association of insertion/deletion polymorphism of angiotensin-converting enzyme gene among Malay male hypertensive infjects in response to ACE inhibitors. JRAAS - J Renin-Angiotensin-Aldosterone Syst. 2015;16(4):872-9. https://doi.org/10.1177/1470320314538878
33. Gunal O, Sezer O, Ustun GU, et al. Angiotensin-converting enzyme-1 gene insertion/deletion polymorphism may be associated with COVID-19 clinical severity: A prospective cohort study. Ann Saudi Med. 2021;41(3):141-6. https://doi.org/10.5144/0256- 4947.2021.141
34. Delanghe JR, Speeckaert MM, De Buyzere ML. COVID-19 infections are also affected by human ACE1 D/I polymorphism. Clin Chem Lab Med. 2020;58(7):1125-6. https://doi.org/10.1515/cclm-2020-0425
35. Gemmati D, Tisato V. Genetic hypothesis and pharmacogenetics side of renin-angiotensin-system in COVID-19. Genes (Basel). 2020;11(9):1-17. https://doi.org/10.3390/genes11091044
36. Park HY, Lee JH, Lim NK, et al. Presenting characteristics and clinical outcome of patients with COVID-19 in South Korea: A nationwide retrospective observational study. Lancet Reg Heal - West Pacific. 2020;5:100061. https://doi.org/10.1016/j. lanwpc.2020.100061
37. Li X, Xu S, Yu M, et al. Risk factors for severity and mortality in adult COVID-19 inpatients in Wuhan. J Allergy Clin Immunol. 2020;146(110-8):109-18. https://doi.org/10.1016/j.jaci.2020.04.006
38. Smits SL, De Lang A, Van Den Brand JMA, et al. Exacerbated innate host response to SARS-CoV in aged non-human primates. PLoS Pathog. 2010; 6(2):e1000756. https://doi.org/10.1371/journal.ppat.1000756
39. Ismail SNA, Abdul Halim Zaki I, Noordin ZM, et al. Clinical characteristics and risk factors for mortality in patients with COVID-19: A retrospective nationwide study in Malaysia. Proc Singapore Healthc. 2022;0(0):1-8. https://doi. org/10.1177/20101058221085743
40. Aung AK, Aitken T, Teh BM, et al. Angiotensin converting enzyme genotypes and mortality from COVID-19: An ecological study. J Infect. 2020;81(January):961-5. https://doi.org/10.1016/j.jinf.2020.11.012
41. Liu M, Yi J, Tang W. Association between angiotensin converting enzyme gene polymorphism and essential hypertension: A systematic review and meta-analysis. JRAAS - J Renin-Angiotensin-Aldosterone Syst. 2021;22(1):1-12. https://doi. org/10.1177/1470320321995074
42. Chen N, Zhou M, Dong X, et al. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. Lancet. 2020;395(10223):507-13. http://dx.doi.org/10.1016/S0140-6736(20)30211-7
43. Li G, Fan Y, Lai Y, et al. Coronavirus infections and immune responses. Vol. 92, Journal of Medical Virology. John Wiley and Sons Inc.; 2020;424-32. https://doi.org/10.1002/jmv.25685
44. Huang S, Wang J, Liu F, et al. COVID-19 patients with hypertension have more severe disease: a multicenter retrospective observational study. Hypertens Res. 2020;43(8):824-31. https://doi.org/10.1038/s41440-020-0485-2
45. Deng SQ, Peng HJ. Characteristics of and Public Health Responses to the Coronavirus Disease 2019 Outbreak in China. J Clin Med. 2020;9(2):575. https://doi.org/10.3390/jcm9020575
46. Fuk-Woo Chan J, Yuan S, Kok KH, et al. A familial cluster of pneumonia associated with the 2019 novel coronavirus indicating person-to-person transmission: a study of a family cluster. Lancet. 2020;395:514-23. https://doi.org/10.1016/S0140- 6736(20)30154-9
47. Mutiawati E, Fahriani M, Mamada SS, et al. Anosmia and dysgeusia in SARS-CoV-2 infection: Incidence and effects on COVID-19 severity and mortality, and the possible pathobiology mechanisms - a systematic review and meta-analysis. F1000Research. 2021;10:1-28. https://doi.org/10.12688/f1000research.28393.1
48. Ni W, Yang X, Yang D, et al. Role of angiotensin-converting enzyme 2 ( ACE2 ) in COVID-19. Crit Care. 2020;24(422):1-10. https://doi.org/10.1186/s13054-020-03120-0
49. Duarte-Neto AN, Caldini EG, Gomes-Gouvêa MS, et al. An autopsy study of the spectrum of severe COVID-19 in children: From SARS to different phenotypes of MIS-C. EClinicalMedicine. 2021;35(2021):100850. https://doi.org/10.1016/j. eclinm.2021.100850
50. Mondello C, Roccuzzo S, Malfa O, et al. Pathological Findings in COVID-19 as a Tool to Define SARS-CoV-2 Pathogenesis. A Systematic Review. Front Pharmacol. 2021;12(April):614586. https://doi.org/10.3389/fphar.2021.614586
51. Kim SG, Sung HH. Status of Kidney Function in Hospitalised COVID-19 Patients in the Southern Gyeonggi Province, South Korea. Korean J Clin Lab Sci. 2021;53(3):208-16. https://doi.org/10.15324/kjcls.2021.53.3.208
52. Liu YF, Zhang Z, Pan XL, et al. The chronic kidney disease and acute kidney injury involvement in COVID-19 pandemic: A systematic review and meta-analysis. PLoS One. 2021;16(1):e0244779. https://doi.org/10.1371/JOURNAL.PONE.0244779
53. Xu W, Huang C, Fei L, et al. Dynamic changes in liver function tests and their correlation with illness severity and mortality in patients with covid-19: A retrospective cohort study. Clin Interv Aging. 2021;16:675-85. http://doi.org/10.2147/CIA.S303629
54. Harapan H, Fajar JK, Supriono S, et al. The prevalence, predictors and outcomes of acute liver injury among patients with COVID-19: A systematic review and meta-analysis. Rev Med Virol. 2022;32(3). https://doi.org/10.1002/rmv.2304
55. Yang Y, Xiao Z, Ye K, et al. SARS-CoV-2: characteristics and current advances in research. Virol J. 2020;17(1):1-17. https://doi. Org/10.1186/s12985-020-01369-z

Most read articles by the same author(s)

1 2 3 4 5 6 7 8 9 10 > >>