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.

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.

Lack of association between the eNOS rs1800779 (A/G) polymorphism and the myocardial infarction incidence among the Iraqi Kurdish population.

Objectives: The genetic polymorphisms of the endothelial nitric oxide synthase (eNOS) gene are strongly associated with several cardiovascular diseases (CVDs) in various populations. The current study aimed to investigate the association of the eNOS rs1800779 (A/G) polymorphism with the progress of myocardial infarction (MI). Methods: Eighty-five healthy subjects and 80 patients with MI admitted to the Erbil Cardiac Centre in the Kurdistan Region of Iraq were enrolled in the study. All participants were Kurdish from the same ethnic group. The amplification refractory mutation system polymerase chain reaction (ARMS-PCR) was used to determine the rs1800779 (A/G) polymorphism of eNOS, and the nitric oxide (NO) serum level was detected by spectrophotometer. Results: The genotypic frequencies of the eNOS rs1800779 AA (wild type), AG, and GG were 58.75%, 33.75%, and 7.50%, respectively, in the MI patients, and 49.41%, 43.53%, and 7.06%, respectively, for the control group. The frequencies of the A and the G alleles were 75.6% and 24.4%, respectively, in the MI group, and 71.2% and 28.8%, respectively, in the control subjects. The results revealed a lack of association of the rs1800779 genotype distribution with the level of NO serum and increased risk of MI. Conclusion: The study concluded that there is a lack of association between the genotypes and alleles of the rs1800779 eNOS and susceptibility to MI in the studied population.