ABSTRACT
Objective: COVID-19 is a serious respiratory and vascular disease that impairs the protective function of the endothelial barrier. Endothelial nitric oxide synthase (eNOS), the most important isoform for nitric oxide (NO) production, is mostly expressed in endothelial cells. Therefore, this study aims to evaluate whether eNOS G894T and variable tandem repeat number (VNTR) functional variants show predisposition to developing COVID-19. Materials and Methods: The study includes a total of 384 subjects (284 COVID-19 patients and 100 healthy controls). Two eNOS gene variants (G894T and VNTR) were genotyped using the polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) methods, with the results being evaluated using statistical methods. Results: A significant association has been identified between eNOS G894T and COVID-19. For the eNOS G894T variant, the T/T genotype (p=0.035) and T allele carriers (p=0.030) appear to have an increased risk of developing COVID-19. The eNOS G894T G/G genotype (p=0.030) was more common in the control group compared to the patient group. No significant difference was found between groups regarding the eNOS VNTR genotype and allele frequencies (p>0.05). The genotypes of the patient and control groups for these variants were in Hardy-Weinburg equilibrium (HWE). Conclusion: These results provide evidence supporting the hypothesis that the eNOS G894T variant is associated with an increased risk of developing COVID-19 in the Turkish population. These findings may lead to the emergence of new treatment options. Further research is required to understand the molecular mechanisms involved in the pathogenesis of the disease. © 2023 The authors.
ABSTRACT
OBJECTIVE: Coronavirus disease 2019 (COVID-19) has rapidly spread worldwide and presents critical challenges for public health. Due to its chronic and systemic course, COVID-19 is currently accepted as a multi-systemic infectious disease. Here we explore the possible association between disease course and hereditary thrombotic factors and comorbidities. PATIENTS AND METHODS: The patients admitted to the COVID-19 center in the Istanbul Faculty of Medicine were recruited for the study. The patients were classified according to the clinical course, severe vs. mild. Five polymorphic loci were analyzed by multiplex PCR: Factor V Leiden (FVL), FII G20210A, Beta-fibrinogen G-455A, and methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C. RESULTS: FII G20210A and Beta-fibrinogen G-455A genotypes were significantly higher in the study group compared to the literature. Wildtype genotype (GG) in Factor V Leiden locus was significantly associated with low D-Dimer levels (p =0.013). The GA genotype increased the D-Dimer levels 2.55-times compared to the GG genotype (p =0.003). Moreover, the Beta-fibrinogen G-455G genotype was significantly higher in the LDH>250 group (p =0.046). CONCLUSIONS: The presence of solid tumors in patients with COVID-19 was related to the severity of the disease course. No evidence of a correlation between the severity of the disease and all five thrombotic mutations was found, whereas the FII G20210A and Beta-fibrinogen G-455A mutations were significantly high compared to previously reported Turkish population data and global carrier rates. This finding will need to be verified by further studies with larger samples since it may reflect a likelihood of having the COVID-19 disease. The high carrier frequency of FVL mutation was more likely present in the D-dimer high group generating an increase in the D-dimer levels 2.55-times compared to the wildtype.