Impact of cytokines genes polymorphisms and their serum levels on childhood asthma in Egyptian population.

BACKGROUND: Asthma is chronic immune-mediated airway inflammation, and it is affected by a complex network of interacting cytokines. To date, the exact role of each cytokine and its genetic polymorphisms in childhood asthma development and its severity has remained poorly understood. The purpose of this study was to explore potential roles of four cytokine genes polymorphism and serum levels l [(T helper-2 (Th2) cytokine); Interleukin-4 (IL-4) 590, (Th3 cytokine); and transforming growth factor ß1 (TGF-ß1) 509T; (Th17) including tumor necrosis factor-alpha (TNF-α), and IL17A rs8193036] in childhood asthma risk and control in Egyptian children, for the 1st time. MATERIALS AND METHODS: This case-control study included two children subgroups; Group1 included 216 non-asthmatic controls and (Group 2) 216 cases diagnosed with asthma (clinically and spirometry-based) were classified as controlled, partly controlled, and uncontrolled. Polymorphisms of TGF-ß1-509, IL-4 590, and TNF-α-308 genes were detected using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). IL-17 was genotyped using tetra-primer amplification refractory mutation system polymerase chain reaction (ARMS-PCR). Serum cytokines levels were measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: Serum total IgE, TGF-ß1, IL4, TNF-α, and IL17A levels were significantly higher in asthmatic compared to controls. Also, significant increases in serum total IgE, IL-4, TGF-ß1, and TNF-α levels are combined with poor asthma control, while no significant IL17A changes. There were significant changes of IL-4-590, TNF-α-308, and IL17A genotypes and allele distributions between asthmatic and controls groups as well as different asthma control levels; while no impact of TGF-ß1 SNP on asthma risk and control level. Four cytokines SNPs affected their serum levels among asthmatic patients. CONCLUSION: There are impacts of cytokine gene polymorphisms (IL-4-590, TNF-α-308, and IL17A); but not TGF-ß1 on asthma susceptibility and poor asthma control in Egyptian children.

Proviral Integration of Moloney Virus-2 (PIM-2) Expression Level as a Prognostic Marker in Patients with Acute Myeloid Leukemia.

Purpose: This study aimed to assess PIM-2 gene expression level as a prognostic marker in AML patients and to correlate the results with their clinical outcome. Patients and Methods: This study was conducted on 50 de novo younger AML patients (median age 44). Quantitative real-time polymerase chain reaction (QRT-PCR) was used to assess the expression level of the PIM-2 gene. The transcription level of the target gene (PIM-2) was normalized to that of the reference gene (GAPDH). Twenty control samples were withdrawn from 20 age- and sex-matched individuals for the analysis of the results using the 2-ΔΔCT method. On day 28 following induction chemotherapy, patients' bone marrow (BM) was examined for evaluation of their remission status. Results: PIM-2 gene expression was higher among AML patients who did not achieve complete remission (CR); also, it was higher in patients in the intermediate and poor cytogenetic risk groups. A significant positive correlation was found between PIM-2 level and BM blasts on day 28. In AML patients, PIM-2 has been discovered to be an independent predictive factor for achieving CR following standard induction treatment. Receiver operating characteristic curve (ROC) and area under the curve (AUC) were performed for PIM-2 level at diagnosis to evaluate its role in achieving remission after induction. It was found that PIM-2 at cutoff ≤1.6 had an AUC (0.903) with a sensitivity (90.48%) and specificity (86.21%), P <0.001. Conclusion: Overexpression of the PIM-2 gene is associated with induction failure and low CR.