A Multicentric Study of ACE2 rs2285666 Polymorphism: The Association with COVID-19 in the Iranian Population

Background: Clinical studies have shown that variations in the ACE2 gene can influence susceptibility to and the severity of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infections. Although the evidence is not conclusive, recent studies have suggested a potential link between the ACE2 rs2285666 polymorphism and COVID-19. Objectives: This multicentric clinical study, conducted in Lorestan and Golestan provinces, aimed to examine the association between the ACE2 rs2285666 polymorphism and COVID-19 in Iranians of various ethnicities, including Fars, Lur, Turkmen, and Balooch. Methods: A total of 372 participants were evaluated, with 201 testing positive for SARS-CoV-2 and 171 negative. The PCR-based restriction fragment length polymorphism (PCR-RFLP) technique, using the AluI enzyme, was employed to identify the polymorphism. Demographic and clinical data were analyzed using IBM SPSS. Hazards were assessed through odds ratio analysis, while Hardy-Weinberg equilibrium (HWE) and genotype variations were evaluated using SNPSTATS. Results: PCR-RFLP analysis indicated that the AA genotype may increase susceptibility to COVID-19. Among female COVID-19-positive patients, 56%, 29%, and 15% exhibited GG, GA, and AA genotypes, respectively, compared to 61%, 35%, and 4% in the control group. In male individuals, the frequencies of G and A genotypes were 89% and 11% in the healthy group, while they were 25% and 75%, respectively, in the patient group. Polymorphism frequencies were not in HWE in both the positive and negative groups (P < 0.05). Logistic regression analysis showed that the AA genotype differed in co-dominant and recessive inheritance models, with odds ratios (OR) of OR = 4.06 (1.10 - 15.00) and OR = 4.21 (1.16 - 15.24). The ACE2 rs2285666 AA or A genotype was strongly associated with an increased risk of COVID-19 in this study. Conclusions: A significant difference in the distribution of the AA and A genotypes was observed in COVID-19 patients. Further studies involving larger and more diverse populations are necessary to explore the impact of this polymorphism on the susceptibility to and severity of COVID-19.