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.