ASSOCIATING eNOS GENE VARIANTS WITH COVID-19 SUSCEPTIBILITY IN THE TURKISH POPULATION

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.

Association of Tumor Necrosis Factor-Alpha (TNF-alpha) and Suppressor of Cytokine Signaling-1 (SOCS-1) Gene Variants in Children with COVID-19

Objective The suppressor of cytokine signaling-1 (SOCS-1) gene is an essential physiological regulator of cytokine signaling. Tumor necrosis factor-alpha (TNF-alpha) is an important component of the immunological response. Herein, we aimed to investigate the effects of SOCS-1 (-1478 CA > Del) and TNF-alpha (-308) polymorphisms on disease susceptibility and prognosis in pediatric patients with coronavirus disease 2019 (COVID-19). Methods One-hundred fifty COVID-19 patients in the COVID-19 emergency department between September 2020 and April 2021 and 80 healthy volunteers (control group) without any additional disease were included. Baseline gene polymorphisms were compared between the patient and healthy control groups. Afterward, the gene polymorphism distribution was examined by forming two separate clinical patients' subgroups. Results While CA/CA and CA/Del gene variants of SOCS-1 were higher in the patient group, Del/Del genotype was more common in the control group (p < 0.05). The GG genotype of the TNF-alpha was significantly more common in the severe subgroup (p = 0.044). The GA genotype of TNF-alpha was associated with the risk of hospitalization (2.83-fold), while the GG genotype was found to be protective in terms of hospitalization (2.95-fold). Conclusions This study will be a guide in terms of the presence of high cytokine release genotypes and COVID-19-related cytokine release syndromes. Copyright © 2023 Georg Thieme Verlag. All rights reserved.

The effect of hereditary thrombotic factors and comorbidities on the severity of COVID-19 disease.

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.

Mannose binding lectin gene 2 (MBL2) variant may contribute to development and severity of COVID-19 infection

Objective: The interindividual variability of the severity of COVID-19 is still obscure. There is much debates about why some young patients who has no underlying cause had bad outcomes while some elderly patients had good survival rates. We aimed to investigate whether MBL2 gene variant (rs1800450) related to the variable clinical courses. Materials-Methods: 284 PCR-confirmed COVID-19 patients and 100 healthy controls were included in the study. COVID-19 patients were subdivided according to the clinical features and clinical characteristics were analyzed. All patients and controls were examined for c.161G>A;Gly54Asp (rs1800450) variation in exon 1 of the MBL2 gene Results: BB variant of MBL2 was more common among COVID-19 cases compared to controls (p=0.001). BB variant cases followed a more severe course (95% CI=0.06-0.23, p=0.001), demonstrated lower early survival (95% CI=0.01-0.22, p=0.001), had more intensive care need (95% CI=0.03-0.25, p=0.001) when compared to AA variant (95% CI=2.1-13.4, p=0.001;95% CI= 2.5-3.4, p=0.001;95% CI= 0.01-0.22, p=0.001). BB variants had developed a secondary bacterial infection in the course when compared to the other genetic variant types. (95% CI=0.11-0.77, p=0.02) Conclusion: MBL2 BB variant results in the overall absence of MBL2 protein and is related with more severe clinical course of COVID-19 infection.