COVID-19 susceptibility and severity: Potential of ACE1 I/D gene polymorphism (rs4646994) and IFITM3 gene (rs12252) polymorphism among Myanmar people

Background: The COVID-19 pandemic caused by SARS-CoV-2 represents one of the most devastating global health crises. Among the various factors contributing to increased risk, host genomic variation is increasingly recognized as a critical determinant of susceptibility to infection and the diversity of clinical outcomes. Polymorphisms in the ACE1 gene (rs4646994 I/D) and IFITM3 gene (rs12252 T>C) are of particular interest as predictors of clinical phenotypes, as revealed by association studies exploring the genetic basis of COVID-19 manifestations. Objective: To investigate the association of ACE1 I/D and IFITM3 T>C gene variants with susceptibility to and severity of SARS-CoV-2 infection among the Myanmar population. Methods: A case-control study was conducted from 2021 to 2023, involving 150 COVID-19-positive patients and 150 COVID-19-negative controls from Yangon Division. Genomic DNA was extracted from whole blood using the salting-out method. Gene polymorphisms were identified using the PCR-RFLP technique. Data analysis was performed using SPSS version 20.2, with chi-square tests and one-way ANOVA applied as appropriate. Results: The observed genotype frequencies conformed to Hardy-Weinberg equilibrium. The DD genotype and D allele of the ACE1 gene were significantly more frequent in COVID-19 patients than in controls. Similarly, the mutant CC genotype and C allele of the IFITM3 gene were significantly more prevalent among COVID-19 patients. Both ACE1 (DD genotype and D allele) and IFITM3 (CC genotype and C allele) polymorphisms were significantly associated with increased risk of severe COVID-19 infection. Conclusions: Carriers of the DD genotype and D allele of the ACE1 gene, as well as the CC genotype and C allele of the IFITM3 gene, are more likely to exhibit increased susceptibility to and severity of COVID-19. These gene polymorphisms may influence both the incidence and clinical outcome of COVID-19 and could serve as predictive markers for disease risk and severity.