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Background: The P53 tumor suppressor gene plays a pivotal role in maintaining cellular homeostasis by preventing the propagation of genome mutations. P53 in its transcriptionally active form is capable of activating distinct target genes that contribute to either apoptosis or growth arrest, like P21. However, the MDM2 gene is a major negative regulator of P53. Single nucleotide polymorphisms (SNP) in codon Arg72Pro of P53 results in impairment of the tumor suppressor activity of the gene. A similar effect is caused by a SNP in codon 31 of P21. In contrast, a SNP in position 309 of MDM2 results in increased expression due to substitution of thymine by guanine. All three polymorphisms have been associated with increased risk of tumorigenesis. Aim of the study: We aimed to study the prevalence of SNPs in the P53 pathway involving the three genes, P53, P21 and MDM2, among acute myeloid leukemia (AML) patients and to compare it to apparently normal healthy controls for assessment of impact on risk. Results: We found that the P21 ser31arg heterozygous polymorphism increases the risk of AML (P value=0.017, OR=2.946, 95% CI=1.216-7.134). Although the MDM2 309G allele was itself without affect, it showed a synergistic effect with P21 ser/arg polymorphism (P value=0.003, OR= 6.807, 95% CI= 1.909-24.629). However, the MDM2 309T allele abolish risk effect of the P21 polymorphic allele (P value= 0.71). There is no significant association of P53 arg72pro polymorphism on the risk of AML. Conclusion: We suggest that SNPs in the P53 pathway, especially the P21 ser31arg polymorphism and combined polymorphisms especially the P21/ MDM2 might be genetic susceptibility factors in the pathogenesis of AML.

N-Acetyltransferases (NAT) have been known to modify the risk to a variety of solid tumors. However, the role of NAT2 polymorphism in risk susceptibility to childhood acute lymphoblastic leukemia (ALL) is still not well known. We performed a case-control study to determine if the common NAT2 polymorphisms play a role in altering susceptibility to pediatric ALL. DNA of 92 pediatric ALL patients and 312 healthy controls was analyzed for the NAT2 polymorphisms using the PCR-RFLP method. The wild-type NAT2*4 was encountered in 8.6 % of patients versus 11.8 % of controls (P = 0.23). The rapid acetylators NAT2*12 803A>G, AG, GG, and AG/GG were overrepresented in controls (P = 0.0001; odds ratio (OR) 0.22, 0.19, and 0.21 respectively). NAT2*5D 341T>C and NAT2*11A 481C>T were of comparable frequencies. For their combination, NAT2*5A, a slow acetylator, both TCTT and CCCT were overrepresented in patients (P < 0.001; OR 15.8 and 17.9 respectively). NAT2*5B (803A>G, 341T>C, 481C>T) was overrepresented in controls (P < 0.001; OR 0.12). Apparently, 803A>G ameliorated the combined effect of 341T>C and 481C>T. A similar effect was obtained with NAT2*5C (341T>A, 803A>G) (P < 0.0001; OR 0.11). For slow acetylator NAT2*7A 857G>A, GA and GA/AA were overrepresented in patients (P = 0.009 and 0.01; OR 2.74 and 2.72 respectively). NAT2*13 282C>T, NAT2*6B 590G>A, and NAT2*14A 191G>A were of comparable frequencies. NAT2 282C>A in combination with NAT2 857G>A (NAT2*7B) showed a synergistic effect in patients versus controls (P < 0.0001; OR 3.51). In conclusion, NAT2 gene polymorphism(s) with slow acetylator phenotype is generally associated with the risk of development of ALL in children.

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Objectives: This study aims to investigate hemostatic changes in patients with coronavirus disease (COVID-19) and their relationship to disease severity and survival.Methods: This study included 284 patients with COVID-19 who attended the Security Forces Hospital, Makkah, Saudi Arabia between October 2020 and March 2021, and retrospectively reviewed their demographic, radiological, and laboratory findings. The coagulation profile was assayed at the time of diagnosis for platelet counts using an automated hematology analyzer; Sysmex XN2000 while international normalized ratio (INR), activated partial thromboplastin time (aPTT), fibrinogen, D-dimer, factor VIII, ristocetin cofactor (RiCoF), and von Willebrand factor antigen (VWF-Ag) were measured by Stago kits on a Stago automated coagulation analyzer (STA Compact Max®).Results: In this study, 32.3% of the cases had severe disease, while 8.8% of the cases died. D-dimer, factor VIII, and RiCoF were the only independent predictors of disease severity, with factor VIII and RiCoF having significantly higher areas under the curve (AUCs) than D-dimer (all p &lt; 0.001). Furthermore, age, aPTT, and factor VIII were associated with an increased risk of mortality in multivariate Cox regression analysis, with factor VIII having a higher AUC of 0.98 than aPTT with an optimal cut-off value of &gt;314 IU/dl in predicting mortality. Cases with factor VIII levels &gt;314 IU/dl, compared to those with factor VIII levels &lt;314 IU/dl, were associated with a significantly shorter mean overall survival time (20.08 vs. 31.35 days, p &lt; 0.001), a lower survival rate (30.3% vs. 99.2%, p &lt; 0.001), and a 16.62-fold increased mortality risk.Conclusion: RiCoF is a novel predictor of disease severity in COVID-19, while factor VIII is confirmed as a predictor of severity and mortality in COVID-19 patients and is associated with lower overall survival and increased mortality risk.

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Background: Type1 diabetes mellitus (T1DM) has a multi-factorial pathogenesis; the interplay between genetic susceptibility and environmental factors is thought to provide the fundamental element for the disease. Apart from HLA, more than 50 genetic variants are associated with T1DM. INS-23/Hph1 A>T (rs689) is one of the effective loci with inconsistent reports in the literature. Accordingly, this study was designed to define the frequencies of INS-23/ Hph1 A>T polymorphism and its association with T1DM in Egyptian diabetic children and their non-diabetic family members as compared to healthy controls. Methods: Using polymerase chain reaction-restriction fragment length polymorphism methodology, analysis of insulin gene VNTR polymorphism was performed for 496 samples (91 patients, 179 parents, 130 siblings, and 96 controls); parents and siblings were apparently healthy. Results: INS genotypes and allele frequencies were comparable between patients, non-diabetic siblings, and parents (p = 0.97 and 0.77, respectively). However, the TT/AT genotype and T allele were over-presented in the three family groups compared to controls (p = 0.0015 and 0.0029, respectively). Comparing patients to controls, the T allele is considered a risk factor for the development of TIDM (OR 2.56, 95% CI 1.42-4.62, p = 0.0017). INS-23/Hph1 A>T polymorphism showed concordance between patients and their mothers (Kappa = 0.446, p = 0.000) but not with their fathers (Kappa = 0.031, p = 0.765). Conclusions: INS-23/Hph1 A>T gene polymorphism was shown to be a risk factor for the development of TIDM. This is in agreement with some and in disagreement with other reports. Studies of risk susceptibility factors have to be carried out locally in each community; results cannot be extrapolated from one ethnic group to another.