Determining Predictive Relationships Between <i>AGTR1</i> and <i>ACE2</i> Polymorphisms with Hypertension and COVID-19 in Patients at A Tshwane Academic Hospital

Background: Severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2), the causative agent of Coronavirus disease 2019 (COVID-19), exploits the angioten-sin-converting enzyme 2 (ACE2) for cell entry, implicating the renin–angiotensin sys-tem (RAS) in disease pathogenesis. Hypertension (HT), a major comorbidity, is strongly influenced by genetic factors within RAS, including angiotensin ii receptor type 1 (AGTR1) and ACE2) polymorphisms. However, data on these variants in African pop-ulations remain scarce. This study investigated associations between AGTR1 and ACE2 single nucleotide polymorphisms (SNPs), HT, and COVID-19 severity in patients at A Tshwane Academic Hospital. Methods: We genotyped AGTR1 and ACE2 SNPs in 94 PCR-confirmed COVID-19 pa-tients using Matrix-Assisted Laser Desorption/Ionization Time-Of-Flight (MAL-DI-TOF) mass spectrometry. Clinical data were extracted from hospital records. Ordi-nal logistic regression models assessed relationships between SNPs, HT, and COVID-19 severity. Results: The cohort (mean age 53.9 years; HT prevalence 54.9%) exhibited mild (54.9%), moderate (18.6%), and severe (26.5%) COVID-19. The rs21068092 A genotype was significantly associated with reduced odds of severe disease (OR = 0.39, 95% CI: 0.14–1.08, p = 0.04), suggesting a protective effect. Other SNPs and clinical variables showed no significant associations. Conclusion: This first report on AGTR1 and ACE2 SNP profiles in COVID‑19 patients from Tshwane highlights rs2106809 as a potential protective marker. Age correlated with severity. Larger, multi‑ethnic studies are needed to confirm these findings.