Angiotensin-Converting Enzyme-2 (ACE-2) with Interferon-Induced Transmembrane Protein-3 (IFITM-3) Genetic Variants and Interleukin-6 as Severity and Risk Predictors among COVID-19 Egyptian Population

Amal F Makled; Sahar A M Ali; S S Eldahdouh; Asmaa S Sleem; Maha M Eldahshan; Yara Elsaadawy; Samar S Salman; Asmaa Mohammed Elbrolosy

doi:10.1155/2023/6384208

Angiotensin-Converting Enzyme-2 (ACE-2) with Interferon-Induced Transmembrane Protein-3 (IFITM-3) Genetic Variants and Interleukin-6 as Severity and Risk Predictors among COVID-19 Egyptian Population

Int J Microbiol. 2023 Dec 21:2023:6384208. doi: 10.1155/2023/6384208. eCollection 2023.

Authors

Amal F Makled¹, Sahar A M Ali¹, S S Eldahdouh², Asmaa S Sleem¹, Maha M Eldahshan¹, Yara Elsaadawy³, Samar S Salman⁴, Asmaa Mohammed Elbrolosy¹

Affiliations

¹ Department of Medical Microbiology and Immunology, Faculty of Medicine, Menoufia University, Shebin al Kom, Egypt.
² Department of Chest Diseases and Tuberculosis, Faculty of Medicine, Menoufia University, Shebin al Kom, Egypt.
³ Department of Medical Microbiology and Immunology, Faculty of Medicine, Ain Shams University, Cairo, Egypt.
⁴ Department of Clinical Pathology, Faculty of Medicine, Menoufia University, Shebin al Kom, Egypt.

Abstract

Introduction: The host genetic background is a crucial factor that underlies the interindividual variability of COVID-19 fatality and outcomes. Angiotensin-converting enzyme-2 (ACE-2) and interferon-induced transmembrane protein-3 (IFITM-3) have a key role in viral cell entrance and priming. The evoked immune response will also provide a predictive prognosis for COVID-19 infection. This study aimed to explore the association between ACE-2 and IFITM-3 genotypes and their corresponding allele frequencies with disease severity indices in the Egyptian COVID-19 population. The serum level of interleukin-6, as a biomarker of hyperinflammatory response, and cytokine storm, was correlated with disease progression, single nucleotide polymorphisms (SNPs) of the selected receptors, and treatment response. Methodology. We enrolled 900 COVID-19-confirmed cases and 100 healthy controls. Genomic DNA was extracted from 200 subjects (160 patients selected based on clinical and laboratory data and 40 healthy controls). The ACE-2 rs2285666 and IFITM-3 rs12252 SNPs were genotyped using the TaqMan probe allelic discrimination assay, and the serum IL-6 level was determined by ELISA. Logistic regression analysis was applied to analyze the association between ACE-2 and IFITM-3 genetic variants, IL-6 profile, and COVID-19 severity.

Results: The identified genotypes and their alleles were significantly correlated with COVID-19 clinical deterioration as follows: ACE2 rs2285666 CT + TT, odds ratio (95% confidence interval): 12.136 (2.784-52.896) and IFITM-3 rs12252 AG + GG: 17.276 (3.673-81.249), both p < 0.001. Compared to the controls, the heterozygous and mutant genotypes for both SNPs were considerable risk factors for increased susceptibility to COVID-19. IL-6 levels were significantly correlated with disease progression (p < 0.001).

Conclusion: ACE-2 and IFITM-3 genetic variants are potential predictors of COVID-19 severity, critical outcomes, and post-COVID-19 complications. Together, these SNPs and serum IL-6 levels explain a large proportion of the variability in the severity of COVID-19 infection and its consequences among Egyptian subjects.