SNP (A > G - rs13057211) but not GT(n) polymorphism in HMOX-1 promotor gene is associated with COVID-19 mortality.

INTRODUCTION: COVID-19 causes severe inflammatory respiratory distress syndrome. The global pandemic caused millions of cases of morbidity and mortality worldwide. Patients may present with variable symptoms including dyspnea, fever, and GIT manifestations. The HMOX-1 gene is located on the long (q) arm of chromosome 22 at position 12.3. HMOX-1 is expressed in all mammalian tissues at basal levels and is considered as a stress response enzyme. HMOX-1 has a specific polymorphic site with variable GT(n) repeats at the promotor region. Several authors evaluated the HMOX-1 GT(n) promoter polymorphism in different inflammatory conditions. We evaluated HMOX-1 promoter polymorphism in relation to serum Hemoxygenase level and inflammatory makers (CRP, Ferritin, PCT, IL-6 and D-dimer) in patients affected by SARS-COV-2 disease. SUBJECTS AND METHODS: Ninety patients confirmed to be infected with COVID-19 were followed up till the study end point (recovery and discharge or death). HMOX-1 promotor GT(n) polymorphism was evaluated using Sanger sequencing. HMOX-1 enzyme serum level was measured by ELISA and the level of different inflammatory markers was assessed by available commercial kits. RESULTS: A novel Single nucleotide polymorphism (SNP) (A > G) - rs13057211 in the GT(n) region of HMOX-1 promoter gene was found in 40 (61.5%) COVID-19 patients out of the studied 65 patients. This (A > G) SNP was associated with higher mortality rate in COVID-19 as it was detected in 27 patients (75% of the patients who succumbed to the disease) (p = 0.021, Odds ratio = 3.7; 95% CI:1.29-10.56). Serum IL-6 (Interleuken-6) was positively correlated the length of Hospital Stay (LOHS) and procalcitonin (PCT); (p = 0.014, r: 0.651 and p < 0.001, r:0.997) respectively while negatively correlated with levels of HMOX-1 enzyme serum level (p = 0.013, r: -0.61). CRP correlated positively with LOHS (p = 0.021, r = 0.4), PCT (p = 0.044, r = 0.425) and age (p < 0.001, r = 0.685). Higher levels of D-Dimer and PCT were observed in patients with the long repeat. There was no significant difference between patients who recovered and those who died from COVID-19 as regards HMOX-1 level and GT(n) polymorphism. CONCLUSION: We report a novel SNP (A > G, rs13057211) in the GT(n) region of HMOX-1 promoter gene that was associated with mortality in COVID-19 patients, however no significant difference was found in HMOX-1 serum level or HMOX-1 (GT)n repeats within the studied groups.

Evaluation of serum Nestin and HOTAIR rs12826786 C>T polymorphism as screening tools for breast cancer in Egyptian women.

BACKGROUND: Nestin is a neural stem cell protein that plays an important role in cancer stem cells (CSC) development and proliferation. It has been identified as a marker for newly formed endothelial cells and was shown to be preferentially expressed in basal and myoepithelial cells of the mammary gland. HOTAIR is long intergenic non-coding (linRNA) associated with tumorigenesis through promotion of epithelial-mesenchymal transition (EMT) and stemness as well. HOTAIR gene contains a functioning single nucleotide polymorphic site rs12826786 C>T that has been associated with several cancer types. METHODS: We evaluated serum Nestin and the HOTAIR rs12826786 C>T polymorphism in healthy Egyptian women and those with breast cancer as a possible screening tool to identify patients with breast cancer. Also, we tested the possible association of the two markers with each other and the aggressiveness of the disease. RESULTS: Patients with breast cancer had a median (Min-Max) of serum Nestin 31.3 (6.7-167.3 pg/mL), while control subjects had a median (Min-Max) of serum Nestin 42.3 (25.7-315.95) pg/mL. The best cut-off value for serum Nestin to differentiate normal subjects and patients with breast cancer was 39.9 pg/mL. This cut-off value had a diagnostic sensitivity of 84.8% and specificity of 65.1%. There was a significant difference in the distribution of different alleles in patients with breast cancer than normal subjects (P=0.039 Exact Fisher test). The breast cancer patients group had 23.9% CC, 52.1% CT, and 23.9% TT genotypes, respectively, while the control group had 46.9% CC, 42.8% CT, and 10.2% TT, respectively. CONCLUSIONS: A significantly low serum Nestin below 39.9 pg/mL and a higher percentage of the T/T homozygous variant allele of HOTAIR rs12826786 C>T were found in Egyptian patients with breast cancer. We suggest that the reported cut-off value of serum Nestin and the presence of C/T polymorphism can be used to assess the risk of females for developing breast cancer and might be of potential benefit in screening the disease. Larger studies in different ethnic groups are needed to confirm our findings.

Evaluation of pleural fluid human epididymis 4 (HE4) as a marker of malignant pleural effusion.

Pleural effusion is a commonly encountered problem in clinical practice, and pleural fluid analysis is usually the first step towards identifying the underlying etiology. Numerous studies have been published analyzing the potential utility of measuring biomarkers in pleural fluid as possible indicators of a malignant effusion; however, there are no studies that have examined the presence of human epididymis 4 (HE4) in pleural effusions. The aims of this study were to assess pleural effusion and serum concentrations of HE4 in patients with different types of pleural effusions and to evaluate the diagnostic performance of HE4 in detecting malignant pleural effusion. A prospective cohort study was carried out of 88 consecutive patients presenting with pleural effusions. The patients were divided into three groups: 22 patients with transudative effusions, 32 patients with non-malignant exudative effusions, and 34 patients with malignant pleural effusions. Blood and pleural fluid HE4 levels were measured using immunoassay. Both serum HE4 levels and pleural effusion HE4 levels were significantly higher in patients with malignant effusions than in patients with transudative or non-malignant exudative effusions. A pleural fluid HE4 cutoff value of 1,675 pmol/L was found to predict malignant pleural effusions with a diagnostic sensitivity of 85.3 % and specificity of 90.7 %. The current study reports a novel finding of increased serum and pleural fluid HE4 levels in patients with malignant effusions compared to non-malignant effusions. This finding has the potential to strengthen the diagnostic performance of tumor markers in detecting malignant pleural effusions.

Taq1B polymorphism of cholesteryl ester transfer protein (CETP) in Egyptian patients with metabolic syndrome.

AIM: We aimed at evaluation of the possible association of cholesteryl ester transfer protein (CETP) Taq1B polymorphism with the components of metabolic syndrome in a cohort of Egyptian patients compared to their healthy counterparts. PATIENTS AND METHODS: Blood samples were collected for lipid profile, fasting glucose, insulin and routine biochemical tests. The Taq1B genotypes of CETP were determined using RFLP-PCR technique. RESULTS: The patients group showed a significantly higher B1B1 genotype and lower B2B2 genotype compared to the controls group. Serum HDL-C level was significantly higher in all subjects with the B2B2 genotype compared to those with B1B1 genotype. In the patients group, age positively correlated with cholesterol level, triglycerides, BMI and waist circumference. CONCLUSION: Egyptian patients affected with metabolic syndrome have a higher prevalence of B1B1 genotype that is associated with lower serum HDL-C levels.

Plasma myeloperoxidase, NT-proBNP, and troponin-I in patients on CAPD compared with those on regular hemodialysis.

Myeloperoxidase (MPO) is a hemoprotein that is released during inflammation and may lead to irreversible protein and lipid modification, increasing levels of oxidized low density lipoprotein, and promoting athrogenesis. Recently, it has been considered as a risk factor for cardiovascular diseases. Similarly, the measurement of carotid intima-media thickness gives an indication about the degree of atherosclerosis and prediction of clinical cardiovascular events. Elevated white blood cells counts may indicate a state of acute inflammation and follow its progression. Dialysis patients are at a high risk of developing cardiovascular disease compared with healthy subjects. The role of N-terminal pro-brain natriuretic peptide and increased cardiac troponin in identification and prognostication of cardiovascular diseases in end-stage renal disease patients has been investigated. The current study aimed to evaluate plasma MPO and its possible relationship with carotid intima-media thickness, troponin I, N-terminal pro-brain natriuretic peptide (NT-proBNP), and insulin resistance as measured by homeostatic model assessment (HOMA index) in a cohort of Saudi patients who are undergoing hemodialysis (HD) vs. continuous ambulatory peritoneal dialysis for end-stage renal disease. Plasma MPO was significantly higher in patients on continuous ambulatory peritoneal dialysis (CAPD) than in those on HD and in normal subjects (P<0.001). Conversely, NT-proBNP plasma levels were significantly higher in patients on HD (both predialysis and postdialysis) than in those on CAPD (P<0.01) and than normal subjects. Similarly, plasma troponin-I levels were significantly higher in patients on HD compared with those of CAPD and than normal subjects (P<0.001). Plasma troponin-I and NT-proBNP levels were positively correlated in the 3 groups namely those on CAPD, Pre-HD, and post-HD (r: 0.464 and P=0.047; r: 0.330 and P=0.013; and r: 0.452 and P=0.024), respectively. There was no correlation between the MPO level and carotid intima-media thickness (P>0.05). However, plasma MPO level correlated positively with the white blood cell count in patients on CAPD and in those on HD (P<0.05). Our findings suggest an increased oxidative stress in CAPD patients compared with HD patients, while the reported difference in plasma NT-proBNP and troponin-I may be related to the rapid decline of residual renal function in HD and type of membrane used in the HD dialysis procedure itself.

Possible contribution of serum activin A and IGF-1 in the development of hepatocellular carcinoma in Egyptian patients suffering from combined hepatitis C virus infection and hepatic schistosomiasis.

OBJECTIVES: The present study evaluated the role of activin A, insulin-like growth factor 1 (IGF-1) and insulin-like growth factor binding protein 3 (IGFBP-3) in Egyptian patients suffering from combined hepatitis C virus (HCV) infection and hepatic schistosomiasis. DESIGN AND METHODS: Four groups were included in the present study. Group I: 30 healthy subjects were included as controls; Group II (HCV): 30 patients with chronic liver disease due to HCV infection without evidence of schistosomiasis; Group III (SHF + HCV): 30 patients with combined disease, chronic schistosomal hepatic fibrosis (SHF) and chronic hepatitis C infection; Group IV (HCC): 30 patients with hepatocellular carcinoma associated with chronic hepatitis C virus and schistosomal infection. RESULTS: Patients with HCV, HCV + SHF and those with HCC had a significantly higher serum activin A compared with the control group (P < 0.001). Serum activin A level (mean +/- SD) was 5.7 +/- 2.76, 10.59 +/- 3.59, 15.39 +/- 4.61 and 19.93 +/- 5.43 ng/mL in controls, HCV patients, HCV + SHF patients and HCC patients, respectively. Serum IGF-1 was significantly lower in HCV patients, HCV + SHF patients and HCC patients compared to the control group (P < 0.001). Serum IGF-1 was 121.7 +/- 73.4, 76.7 +/- 23.5, 35.7 +/- 17.6 and 39.9 +/- 25.9 ng/mL in controls, HCV patients, HCV + SHF patients and HCC patients, respectively. Similarly, serum IGFBP-3 was significantly lower in HCV patients, HCV + SHF patients and HCC patients compared to the control group (P < 0.001). Furthermore, serum insulin-like growth factor binding protein 3 (IGFBP-3) was significantly lower in patients with HCC compared to patients with HCV or those with HCV + SHF (P < 0.01 and P = 0.024, respectively). The median (range) of serum IGFBP-3 was 4452 (352.2-8965), 3457 (1114-6000), 2114 (867-5901) and 1202 (576-3994) ng/mL in controls, HCV patients, HCV + SHF patients and HCC patients, respectively. Serum activin A correlated positively with Child-Pugh scoring in patients with HCV, HCV + SHF and those with HCC. The correlation coefficient was significant, at 0.001, in total cases. CONCLUSIONS: We conclude that patients with HCV, HCV + SHF and those with HCC have a significantly higher serum activin A when compared with controls. Serum activin A level was significantly higher in patients with HCV + SHF compared to those with HCV alone (P < 0.01) with a significant positive correlation between the serum activin A level and Child-Pugh scoring in patients with HCV, HCV + SHF and those with HCC. Furthermore, serum IGF-1 and IGFBP-3 levels were significantly reduced in patients with HCV, HCV + SHF and those with HCC compared to the control group. We suggest that this pattern (high activin A and low IGF-1 and its binding protein 3) may play a role in development of HCC in Egyptian patients suffering from combined hepatitis C virus infection and hepatic schistosomiasis.

Diagnostic value of serum procalcitonin and C-reactive protein in Egyptian children with streptococcal tonsillopharyngitis.

We investigated serum procalcitonin (PCT) and C-reactive protein (CRP) in children with streptococcal tonsillopharyngitis or nonstreptococcal tonsillopharyngitis and in healthy children. The median (range) for PCT was 0.374 (0.11-6.5), 0.105 (0.01-0.53) and 0.02 (0.01-0.08) ng/mL in the streptococcal, nonbacterial tonsillopharyngitis and control groups, respectively. PCT had a greater specificity than CRP for detection of bacterial tonsillopharyngitis.