Differential impact of the angiotensin-converting enzyme-2 (ACE2 rs4343 G>A) and miR-196a2 rs11614913 C>T gene alterations in COVID-19 disease severity and mortality

Mohammad Muzaffar Mir; Rashid Mir; Mushabab Ayed Abdullah Alghamdi; Badr Abdulmohsin Alsayed; Imadeldin Elfaki; Ali Al Bshabshe; Rabia Farooq; Muhanad Alhujaily; Muffarah Hamid Alharthi; Mohannad Mohammad S Alamri; Abdullah M Al-Shahrani

doi:10.3892/etm.2022.11345

Differential impact of the angiotensin-converting enzyme-2 (ACE2 rs4343 G>A) and miR-196a2 rs11614913 C>T gene alterations in COVID-19 disease severity and mortality

Exp Ther Med. 2022 Jun;23(6):418. doi: 10.3892/etm.2022.11345. Epub 2022 Apr 29.

Affiliations

¹ Department of Basic Medical Sciences (Biochemistry), College of Medicine, University of Bisha, Bisha 61922, Saudi Arabia.
² Prince Fahd Bin Sultan Research Chair, Department of MLT, Faculty of Applied Medical Sciences, University of Tabuk, Tabuk 71491, Saudi Arabia.
³ Department of Internal Medicine, College of Medicine, University of Bisha, Bisha 61922, Saudi Arabia.
⁴ Department of Internal Medicine, University of Tabuk, Tabuk 71491, Saudi Arabia.
⁵ Department of Biochemistry, University of Tabuk, Tabuk 71491, Saudi Arabia.
⁶ Department of Internal Medicine/Critical Care, College of Medicine King Khalid University, Abha 61421, Saudi Arabia.
⁷ Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, University of Bisha, Bisha 61922, Saudi Arabia.
⁸ Department of Family Medicine, College of Medicine, University of Bisha, Bisha 61922, Saudi Arabia.

Abstract

The recent coronavirus outbreak from Wuhan China in late 2019 caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) resulted in a global pandemic of coronavirus-19 disease (COVID-19). Understating the underlying mechanism of the pathogenesis of coronavirus infection is important not only because it will help in accurate diagnosis and treatment of the infection but also in the production of effective vaccines. The infection begins when SARS-CoV-2 enters the cells through binding of its envelope glycoprotein to angiotensin-converting enzyme2 (ACE2). Gene variations of ACE2 and microRNA (miR)-196 are associated with viral infection and other diseases. The present study investigated the association of the ACE2 rs4343 G>A and miR-196a2 rs11614913 C>T gene polymorphisms with severity and mortality of COVID-19 using amplification refractory mutation system PCR in 117 COVID-19 patients and 103 healthy controls from three regions of Saudi Arabia. The results showed that ACE2 rs4343 GA genotype was associated with severity of COVID-19 (OR=2.10, P-value 0.0028) and ACE2 rs4343 GA was associated with increased mortality with OR=3.44, P-value 0.0028. A strong correlation between the ACE2 rs4343 G>A genotype distribution among COVID-19 patients was reported with respect to their comorbid conditions including sex (P<0.023), coronary artery disease (P<0.0001), oxygen saturation <60 mm Hg (P<0.0009) and antiviral therapy (0.003). The results also showed that the CT genotype and T allele of the miR-196a2 rs11614913 C>T were associated with decreased risk to COVID-19 with OR=0.76, P=0.006 and OR=0.54, P=0.005, respectively. These results need to be validated with future molecular genetic studies in a larger sample size and different populations.

Keywords: COVID-19 mortality; COVID-19 severity; angiotensin-converting enzyme2; coronavirus infection; coronavirus-19 disease; gene polymorphism; microRNA196a2; pathogenesis; severe acute respiratory syndrome coronavirus-2; susceptibility to SARS-CoV-2.

Grants and funding

Funding: The authors extend their appreciation to the Deputyship for Research and Innovation, Ministry of Education in Saudi Arabia for funding this research work through the project number UB-47-1442.