The impact of MCP1-2518A/G and CCR2-V64I genetic polymorphisms in Egyptian sickle cell disease patients.

BACKGROUND: Sickle cell disease (SCD) is an inherited genetic disorders of hemoglobin that causes multisystem morbidity. The pathophysiology of SCD is complex and includes HbS polymerization/sickling, hemolysis, endothelial dysfunction and inflammation. Chemokines are proteins playing an important role in the inflammation process and could be involved the context of pro-inflammatory SCD. Some chemokine polymorphism were found to be associated with clinical complication in SCD. AIM OF THE STUDY: Was to explore the frequency and the possible effect of Monocyte Chemo-attractant Protein 1-2518A/G (MCP1-2518A/G) and Chemokine Receptor 2-V64I (CCR2-V64I) genetic polymorphisms on clinical and laboratory disease-related variables in Egyptian Sickle cell disease patients. PATIENTS AND METHODS: Genotyping of the two genes were performed by PCR-RFLP technique for 80 SCD patients as well as 50 healthy control group. RESULTS: The study revealed that the MCP1-2518 polymorphic genotypes (AG & GG) showed no statistically significant difference in the distribution of the polymorphic genotypes between SCD patients and the controls (p = 0.164). While a significantly higher frequency of the mutant variants CCR2-V64I GA/AA among SCD patients than the control subjects were found (p = 0.032). Regarding the clinic-pathological features, the frequency of recurrent infections, vaso-occlusive crisis, severe vaso-occlusive crisis and number of hospitalization/year were higher in patients harbouring the MCP1-2518A/G and CCR2-V64I polymorphic genotypes than the wild genotype, and gall bladder complications were higher in MCP1-2518 G allele patients, whereas surgical splenectomy were higher in CCR2-V64I A allele patients (p < 0.05). IN CONCLUSION: MCP1-2518A/G and CCR2-V64I genetic polymorphisms may influence the clinical severity of sickle cell disease.

The Development of FVIII Inhibitors in Relation to IL10 Gene Polymorphism in Hemophilia A Egyptian Pediatric Patients.

BACKGROUND: Development of inhibitors against Factor VIII (FVIII) in hemophilia A patients is a serious complication of therapy. Many cytokines, including interleukin-10 (IL10), may affect inhibitor development; however, literature data are not sufficient to prove this association. The aim of this study was to investigate the relation between FVIII inhibitor formation and IL10-1082A/G polymorphism among Egyptian hemophiliacs. METHODS: Patients were screened for FVIII inhibitors using the Bethesda method. IL10-1082A/G polymorphism was detected by polymerase chain reaction-restriction fragment length polymorphism. RESULTS: Six patients (12%) developed inhibitors. No statistically significant difference was found between inhibitor positive and negative patients regarding IL10-1082A/G genotypes, disease severity, or treatment-related variables (type of FVIII received, treatment regimen, age at first exposure to FVIII, and frequency of replacement therapy). CONCLUSIONS: FVIII inhibitor formation in this group of Egyptian hemophiliacs was not correlated to IL10-1082A/G polymorphism, disease severity, or any of the treatment variables.

TAp73 and ΔNp73 relative expression in Egyptian patients with lymphoid neoplasms.

BACKGROUND AND AIMS: The p73 gene has different isoforms with opposing anti- and pro-apoptotic functions. The pro-apoptotic activities are inhibited by overexpression of the dominant ΔNp73 isoform. The aim of this study was to detect the expression of the TAp73 and ΔNp73 isoforms in Egyptian patients with malignant lymphoid neoplasms. Their expression was analyzed by quantitative RT-PCR. PATIENTS AND METHODS: The study included 30 B-NHL patients, 24 T-NHL patients, 16 ALL patients, 18 CLL patients, 22 patients with reactive lymphoid hyperplasia, and 6 healthy control subjects. RESULTS: ALL and CLL patients expressed both isoforms at higher levels compared to lymphoma patients. Higher expression of TAp73 was found in both B-NHL and T-NHL (around 4-fold and 16-fold, respectively) in comparison to ΔNp73 (2-fold and 14-fold, respectively). In CLL patients both isoforms showed higher expression levels in comparison to normal peripheral blood lymphocytes controls: nearly 27-fold for TAp73 and 233-fold for ΔNp73. All ALL patients showed higher expression of both studied isoforms than controls (9-fold for TAp73 and 386-fold for ΔNp73). The highest ΔNp73 expression along with a higher ΔNp73/TAp73 ratio (67-fold) was found in ALL patients compared with CLL patients (21-fold). CONCLUSIONS: A considerable number of lymphoma patients lacked the expression of either or both isoforms, while all lymphoid leukemia patients expressed both isoforms. The expression pattern differences of p73 isoforms may reflect differences in the biology of these malignancies.

Molecular and serological assessment of parvovirus B-19 infection in Egyptian children with sickle cell disease.

BACKGROUND/PURPOSE: Human parvovirus B-19 (PB-19) is a cause of hemolysis, red blood cell aplasia, and severe conditions in patients with sickle cell anemia, but the molecular mechanisms of the infection are still insufficiently understood. This study aimed to detect PB-19 DNA together with its antibodies in the sera of Egyptian children with sickle cell disease and to assess the contribution of this infection, which causes transient cessation of erythropoiesis, in precipitating severe anemia in some cases. METHODS: One hundred children with sickle cell disease seeking medical advice in the pediatric-hematology clinic were recruited. Sera of the patients were compared with those of 60 healthy children regarding the presence of PB-19 immunoglobulin (Ig)G and IgM as well as detection of its DNA by nested-polymerase chain reaction technique. RESULTS: There were statistically significant differences in the prevalence of PB-19 IgM, IgG, and DNA among patients when compared with controls (p < 0.001, p = 0.001, and p < 0.001 respectively). Acute PB-19 infection detected by positive IgM and DNA was found in 30% of the patients, while chronic PB-19 infection detected by positive IgG and DNA was detected in 24% of the patients. Anemia was worse in children with acute PB-19 infection than in those with chronic infection, while anemia was mild in children with old infection. CONCLUSION: PB-19 infection is detected at high rates among Egyptian children with sickle cell disease and it may result in severe anemia. So, PB-19 must be suspected and screened for in such group of patients.