Mona El-Ghamrawy

DNA methyltransferase 3B (DNMT3B -579G>T) promotor polymorphism and the susceptibility to pediatric immune thrombocytopenic purpura in Egypt.

Idiopathic thrombocytopenic purpura (ITP) is an autoimmune disease characterized by increased platelet destruction. Although the etiology of ITP remains unclear, it is accepted that both environmental and genetic factors play an important role in the development of the disease. The present study aimed at exploring a novel molecular determinant that may influence the susceptibility and course of ITP in Egyptian children. To achieve our aim, genotyping of DNMT3B -579G>T promotor polymorphism by polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) assay. The current study was conducted on 140 ITP patients and 150 age and gender matched healthy controls. The results obtained revealed that DNMT3B -579 TT homotype was significantly higher in ITP patients and conferred almost three fold increased risk of ITP (OR=3.16, 95%CI=1.73-5.79). There was no statistically significant difference between ITP patients with wild or mutant genotypes as regards their clinical or laboratory data. Furthermore, there was no statistical difference in the distribution of DNMT3B -579G>T genotypes between acute and chronic ITP patients. In conclusion, DNMT3B -579G>T promotor polymorphism represents a novel genetic risk factor for ITP but not a predictor for tendency to chronicity in pediatric ITP in Egypt.

Glutathione S-Transferase Gene Polymorphisms (GSTM1, GSTT1, and GSTP1) in Egyptian Pediatric Patients with Sickle Cell Disease

Sickle cell disease (SCD) complications are associated with oxidative stress. Glutathione S-transferases (GSTs) are a group of enzymes that protect against oxidative stress. The aims of this study was to evaluate the prevalence of GSTM1, GSTT1, and GSTP1 gene polymorphisms among homozygous sickle cell anemia patients and to investigate the possible association between the presence of these polymorphisms and SCD severity and complications. Genotyping the polymorphisms in GSTT1 and GSTM1 genes was performed using the multiplex polymerase chain reaction (PCR) method. The GSTP1 ILe105Val polymorphism was determined using PCR–restriction fragment length polymorphism. GSTM1 null genotype was significantly associated with increased risk of severe vaso-occlusive crises (VOC) (odds ratio = 1.52, 95% confidence interval = 0.42–5.56, P = 0.005). We found no significant association between GST genotypes and frequency of sickle cell–related pain, transfusion frequency, disease severity, or hydroxyurea treatment. GSTM1 gene polymorphism may be associated with risk of severe VOC among Egyptian SCD patients.

Protein Z and Endothelin‐1 genetic polymorphisms in pediatric Egyptian sickle cell disease patients

Sickle cell disease (SCD) is a monogenic disease associated with multisystem morbidity. Vasculopathy caused by delicate imbalance between coagulation and endothelial systems plays a pivotal role in disease course. As Protein Z and Endothelin‐1 genetic polymorphisms may increase the thrombotic risk, the aim of the current work was to verify the possible impact of Protein Z (PROZ G79A) and Endothelin‐1 (EDN1 G5665T) polymorphisms on the clinic‐laboratory features of the SCD in a cohort of Egyptian pediatric patients.

Association between Duffy antigen receptor expression and disease severity in sickle cell disease patients

Objectives: Sickle cell disease (SCD) is associated with a pro-inflammatory state, characterized by an elevated baseline leukocyte count and inflammatory cytokines. Inflammation, white blood cell (WBC) adhesion to vascular endothelium with subsequent endothelial injury, and repeated ischemia–reperfusion injury contribute to disease pathogenesis. Identification of genetic polymorphisms that may modulate disease severity in SCD is becoming a field of interest. The Duffy blood group antigen has been identified as a receptor for various chemokines involved in neutrophil activation and trafficking. This study aimed at investigating the effect of RBCs’ Duffy antigen expression and its genetic polymorphisms on modulating disease severity and its complications among Egyptian sickle cell patients. Methods We analyzed the association of Duffy genotypes and phenotypes with clinical expression of SCD in 100 Egyptian patients. The Duffy phenotype expression was detected by indirect anti-globulin test while Duffy genotyping was conducted with polymerase chain reaction-restriction fragment length polymorphism-based assay. Results Total WBC count was strongly associated with Duffy genotype. WBCs were significantly higher in Duffy-positive patients (P = 0.002). No statistical significance was evident between individual measures of disease severity (pulmonary dysfunction, avascular necrosis, central nervous system dysfunction, kidney dysfunction, and leg ulcers) and Duffy genotype. Conclusion Our study suggests that RBC Duffy expression increases levels of WBCs in SCD patients and that Duffy genotype may not be a potential biomarker for end-organ damage in SCD.

Interleukin-23R gene polymorphism in pediatric Egyptian patients with primary immune thrombocytopenia.

Primary immune thrombocytopenia is an acquired autoimmune disorder caused by the production of antiplatelet antibodies. These autoantibodies opsonize platelets for splenic clearance, resulting in low levels of circulating platelets. The current case–control study aimed at detecting the frequency of interleukin-23 receptor rs1884444 single nucleotide polymorphism in Egyptian children with primary immune thrombocytopenia and its possible role as a genetic marker for disease risk. Interleukin-23 receptor rs1884444 single nucleotide polymorphism was studied in 50 patients with primary immune thrombocytopenia and 100 healthy age and sex-matched controls by polymerase chain reaction amplification of the target gene followed by allele-specific restriction enzyme digestion. Regarding the distribution of the genotypes of the interleukin-23 receptor rs1884444 polymorphism, no statistically significant difference was found between cases and control groups. The variant genotypes (GT/TT) frequency was 10% in primary immune thrombocytopenia cases versus 7% in the control groups [P value = 0.755, odds ratio (OR): 0.326, 95% confidence interval (CI): 0.099–1.076]. Similarly, no difference was found between acute and chronic cases. The variant genotypes GT/TT frequency was 10.7% in acute versus 9.1% in chronic primary immune thrombocytopenia (P value = 0.849). The variant genotypes GT/TT were not found to be a risk factor for acute primary (P value = 0.807, OR: 0.641, 95% CI: 0.16–2.563) or chronic primary immune thrombocytopenia (P value = 0.914, OR: 0.762, 95% CI: 0.153–3.797). Our study suggests the possibility that interleukin-23 receptor gene polymorphism may not contribute to the susceptibility of development of primary immune thrombocytopenia in Egyptian children.