Background: Many loci were found to be associated with type 2 diabetes mellitus (T2DM) risk as single nucleotide polymorphism (SNP) at the transcription factor 7-like 2 gene (TCF7L2) locus on chromosome 10q (rs7903146) [C/T]. Aim: Estimation of the association of this gene polymorphism with T2DM and its complications in Egyptian population. Patients and Methods: This study was done, using 90 Egyptian T2DM patients and 100 controls. This polymorphism was genotyped by conventional PCR. Measurement of blood glucose, glycated hemoglobin (HbA 1c), lipid profile, and microalbuminuria were performed for the study subjects using standard methods. Body Mass index and fundus examination for detection of diabetic retinopathy were also done. Results: The genotype and allele frequencies in TCF7L2 rs7903146 were nearly the same in the patient and control groups (P > 0.05).Odds Ratio for the high risk allele (T) of (rs7903146) was (OR) = 0.97 with 95% confidence interval (CI) from 0.61 to 1.54 with the P = 0.9. Conclusion: These data suggest that the TCF7L2 SNP rs7903146 may not significantly contribute to T2DM susceptibility in Egyptian population.
Introduction. The coronavirus disease 2019 (COVID-19) pandemic, which emerged in China at the end of 2019, rapidly spread worldwide. The angiotensin-converting enzyme (ACE) gene contains an insertion/deletion (I/D) polymorphism that leads to a higher serum ACE level which is associated with several diseases and also with a high mortality rate in SARS. Therefore, this study aimed at assessing the association between ACE gene polymorphism and the risk and severity of COVID-19 disease in patients. Methodology. Forty-five SARS-CoV-2 infected patients and another random control group of 45 healthy individuals were included. The detection of ACE I/D gene polymorphism in both groups was done by PCR. Results. 53% of infected patients with SARS-CoV-2 had an ACE deletion/deletion genotype (D/D), 27% had an ACE deletion/insertion genotype (D/I), and 20% had an ACE insertion/insertion genotype (I/I). On the one hand, the D/D variant was significantly detected in the COVID-19 patients compared to the control subjects, whereas the I/I variant was significantly detected in the control subjects compared to the COVID-19 patients ( p = 0.004). The D/D variant subgroup showed the lowest lymphocytic count compared to the D/I or I/I subgroups. In addition, the C-reactive protein was significantly higher and the oxygen saturation was significantly lower in patients with the D/D allele compared to the other subgroups. Conclusions. ACE gene polymorphism, particularly the DD genotype, was observed to affect the severity of COVID-19 infection.
Urokinase receptors regulate the interplay between inflammation, immunity, and blood clotting. The soluble urokinase plasminogen activator system is an immunologic regulator affecting endothelial function and its related receptor; the soluble urokinase plasminogen activator receptor (suPAR) has been reported to impact kidney injury. This work aims to measure serum levels of suPAR in COVID-19 patients and correlate the measurements with variable clinicolaboratory parameters and patient outcomes. In this prospective cohort study, 150 COVID-19 patients and 50 controls were included. The circulating suPAR levels were quantified by Enzyme-linked immunosorbent assay (ELISA). Routine COVID-19 laboratory assessments, including CBC, CRP, LDH, serum creatinine, and estimated glomerular filtration rates, were performed. The need for oxygen therapy, CO-RAD score, and survival rates was assessed. Bioinformatic analysis and molecular docking were run to explore the urokinase receptor structure/function and to characterize molecules as potential anti-suPAR therapeutic targets, respectively. We found higher circulating suPAR levels in COVID-19 patients vs. controls (p < 0.001). Circulating suPAR levels positively correlated with COVID-19 severity, the need for O2 therapy, the total leukocytes count, and the neutrophils to lymphocyte ratio, while they were negatively correlated with the O2 saturation level, albumin, blood calcium, lymphocytic count, and GFR. In addition, the suPAR levels were associated with poor prognostic outcomes such as a high incidence of acute kidney injury (AKI) and mortality rate. Kaplan–Meier curves showed a lower survival rate with higher suPAR levels. The logistic regression analysis confirmed the significant association of suPAR levels with the occurrence of AKI related to COVID-19 and with increased mortality probability within three months of COVID-19 follow-up. Some compounds that can act similarly to uPAR were discovered and tested by molecular docking to identify the possible ligand–protein interactions. In conclusion, higher circulating suPAR levels were associated with COVID-19 severity and could be considered a putative predictor of AKI development and mortality.
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