The Association Between ACE I/D and ACE2 rs2285666 Polymorphisms with COVID-19 Disease Severity

<b><i>Background:</i></b> Numerous genetic factors influence the severity and susceptibility to COVID-19. The renin-angiotensin system has a role in the genesis of COVID-19. This study aims to investigate the genetic polymorphisms of Angiotensin-Converting Enzyme Insertion/Deletion (ACE I/D) and ACE2 rs2285666 in patients with COVID-19 and their association with mild, severe, and critical disease symptoms. <b><i>Materials and Methods:</i></b> This study included 300 patients with COVID-19, categorized as mild, severe, and critical. Genotypes for the I/D polymorphism of ACE1 and the rs2285666 polymorphism of ACE2 were determined in all samples using polymerase chain reaction (PCR) and restriction fragment length polymorphism-PCR methodologies, respectively. <b><i>Results:</i></b> This study revealed a significant association between the ACEI/D genotype and the severity of COVID-19 (<i>p</i> < 0.001). A strong association was seen between the frequency of ACEI/D alleles and the severity of COVID-19, with the D allele being more prevalent in the severe and critical cohorts compared with the mild cohort (<i>p</i> < 0.001). A significant association was found between the ACE2 rs2285666 polymorphism and disease severity in both male and female groups (<i>p</i> < 0.05). The frequency of G/A alleles linked to the ACE2 polymorphism exhibited a significant association with disease severity, as the G allele was more common in the severe and critical groups than in the mild group (<i>p</i> = 0.004). <b><i>Conclusion:</i></b> Individuals with the homozygous ACE D/D genotype have an increased susceptibility to severe COVID-19, while the presence of allele I may provide a preventive advantage against severe disease symptoms. The ACE2 rs2285666 variant is associated with disease severity, while the ACE2 G/G genotype is linked to an increased severity of COVID-19.