The severity of COVID-19 in hypertensive patients is associated with mirSNPs in the 3' UTR of ACE2 that associate with miR-3658: In silico and in vitro studies.

Autor:	Safdar M; Department of Breeding and Genetics, Cholistan University of Veterinary and Animal Sciences, Bahawalpur, Pakistan., Ozaslan M; Department of Biology, Division of Molecular Biology and Genetics, Gaziantep University, Gaziantep, Turkey., Mustafa RM; Department of Chemistry, Faculty of Science and Health, Koya University, Koya KOY45, Kurdistan Region - F.R. Iraq.; Volumetric Apparatus and Instrumental Analysis, Modern Surveying Calibration & Testing Labs, Erbil, Kurdistan, Iraq., Smail SW; Department of Biology, College of Science, Salahaddin University-Erbil, Erbil, Iraq.; Department of Medical Microbiology, College of Science, Cihan University-Erbil, Kurdistan Region, Iraq., Khan SS; University Medical and Dental College Faisalabad, Pakistan., Khan MS; Cholistan University of Veterinary and Animal Sciences, Bahawalpur, Pakistan., Akhtar MA; Cardiovascular Research Group, Dept. Medical Biology, UiT-The Arctic University of Norway, Tromsø, Norway., Ali HK; Department of Molecular Biology, Virtual University of Pakistan, Lahore, Pakistan., Younas U; Department of Livestock Management, Cholistan University of Veterinary and Animal Sciences, Bahawalpur, Pakistan., Saeed M; Department of Poultry Science, Cholistan University of Veterinary and Animal Sciences, Bahawalpur, Pakistan., Siddique F; Department of Microbiology, Cholistan University of Veterinary and Animal Sciences, Bahawalpur, Pakistan., Naveed M; Department of Clinical Pharmacology, School of Pharmacy, Nanjing Medical University, Nanjing, P.R China.; Department of Biomedical Sciences, University of Minnesota Medical School, Duluth, MN 55812, USA., Rehman S; State Key Laboratory for Conservation and Utilization of Subtropical Agro-Bioresources of Guangxi University, Nanning, China.
Jazyk:	angličtina
Zdroj:	Journal of Taibah University Medical Sciences [J Taibah Univ Med Sci] 2023 Oct; Vol. 18 (5), pp. 1030-1047. Date of Electronic Publication: 2023 Mar 03.
DOI:	10.1016/j.jtumed.2023.02.009
Abstrakt:	The SARS-CoV-2 virus targets the antigen converting enzyme 2 ( ACE2 ) receptor, thus resulting in elevated morbidity and an increased risk of severe and fatal COVID-19 infection in individuals with hypertension and diabetes mellitus. Objectives: This study aimed to identify the association between increased susceptibility and severity in order to evaluate their impact in hypertensive COVID-19 patients using in vitro and in silico models. Methods: We identified 80 miRNA binding sites on ACE2 (for different miRNAs) as well as various 30 SNPs in the miRNA binding sites of the 3' untranslated region (3' UTR) in the ACE2 gene using different online software and tools. From August 2020 to August 2021, a total of 200 nasopharyngeal/mouth swabs samples were collected from Multan, Pakistan. In order to quantify the cDNA of ACE2 and miR-3658 genes, we used Rotor Gene qRT-PCR on hypertensive patients with COVID-19 as well as healthy controls. Results: Interestingly, the binding site of miR-3658 corresponding to the 3' UTR of ACE2 featured three SNPs (rs1457913029, C>T; rs960535757, A>C, G; rs1423809569, C>T), and its genomic sequence featured a single SNP (rs1024225815, C>T) with the same nucleotide variation (rs1457913029, C>T) which potentially increases the severity of COVID-19. Similarly, three other SNPs (rs1557852115, C>G; rs770335293, A>G; rs1024225815, C>T) were also found on the first binding site positions of miR-3658. Our in vitro study found that ACE2 gene expression had an effect on miR-3658 in COVID-19 patients who also had hypertension. In both cases, our analysis demonstrated that the in silico model captured the same biological mechanisms as the in vitro system. Conclusion: The identified SNPs could represent potential informative signatures owing to their position in the splicing site of the ACE2 gene. (© 2023 [The Author/The Authors].)
Databáze:	MEDLINE
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