Genetic Variations of ferroportin-1(FPN1-8CG), TMPRSS6 (rs855791) and Hemojuvelin (I222N and G320V) Among a Cohort of Egyptian ß-Thalassemia Major Patients.

Iron overload remains a major cause of morbidity and mortality among ß-thalassemia major (ß-TM) patients. Iron regulatory proteins and their genetic variants together with changes in hepcidin levels in thalassemic patients could affect the disease manifestations. This work aimed to study genetic variations of ferroportin-1 (FPN1-8CG), Transmembrane Serine Protease 6 (TMPRSS6 rs855791) and hemojuvelin (HJV I222N and G320V) genes within a cohort of 97 ß-TM Egyptian patients by Polymerase chain reaction Restriction Fragment Length Polymorphism (PCR-RFLP) in comparison to fifty normal control subjects. Among ß-TM patients; the CG variant of FPN1 was significantly higher, while the TT and TC variants of TMPRSS6 were significantly lower in comparison to controls. Liver Iron Concentration (LIC) was significantly higher among ß-TM patients harboring the FPN1 (GG) genotype and we found that FPN1gene mutation acts as independent predictor of MRI LIC (p = 0.011), Pulmonary artery pressure (PAP) was significantly higher in patients harboring the mutant FPN1 (GG and CG) genotypes (p value 0.04). ß-TM patients having the HJV I222N (AA) genotype were having significantly higher cardiac iron overload (p value = 0.026). The studied genetic variants of iron regulatory proteins could alter the manifestations of iron overload thus resulting in different clinical phenotypes of thalassemic patients, these findings need to be confirmed by larger cohorts of patients with longer follow-up periods. Supplementary Information: The online version contains supplementary material available at 10.1007/s12288-022-01580-8.

Combined tumor necrosis factor-α (-308 G/A) and tumor necrosis factor-ß (+ 252 A/G) nucleotide polymorphisms and chronicity in Egyptian children with immune thrombocytopenia.

BACKGROUND: Primary immune thrombocytopenia (ITP) is a common autoimmune disorder. Secretion of TNF-α, TNF-ß and IFN-γ plays a major role in the pathogenesis of ITP. OBJECTIVE: This cross-sectional study aimed to detect TNF-α (-308 G/A) and TNF-ß (+ 252 A/G) gene polymorphism in a cohort of Egyptian children with chronic ITP (cITP) to clarify their possible association with progression to chronic disease. METHODS: The study included 80 Egyptian cITP patients and 100 unrelated age- and sex-matched controls. Genotyping was performed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). RESULTS: Patients with TNF-α homozygous (A/A) genotype had significantly higher mean age, longer disease duration and lower platelet counts (p values 0.005, 0.024 and 0.008, respectively). TNF-α wild (G/G) genotype was significantly more frequent among responders (p = 0.049). Complete response was more frequent among wild (A/A) TNF-ß genotype patients (p = 0.011), and platelet count was significantly lower among homozygous (G/G) genotype (p = 0.018) patients. Combined polymorphisms were strongly associated with susceptibility to chronic ITP. CONCLUSION: Homozygosity in either gene might contribute to a worse course of disease, increased severity and poor response to therapy. Patients expressing combined polymorphisms are more prone to progression to chronic disease, severe thrombocytopenia and longer disease duration.

Association of hereditary antithrombin deficiency with intrauterine growth restriction.

: Antithrombin is a major suppressor of thrombin, factor Xa and blood coagulation. Inherited antithrombin deficiency is rare and is considered among the common causes of inherited thrombophilia. The relationship between antithrombin and IUGR, is questionable. The aim of this study was to trace the relationship between antithrombin deficiency and the intrauterine weight reduction and neonatal morbidity. The study was conducted on 55 full-term neonates (including 25 baby boys and 30 baby girls), all were admitted to Neonatal Intensive Care Unit in Cairo University Hospitals with IUGR; and another 110 healthy full-term neonates as control group. ATIII activities were assessed in citrated of patient and control samples automatically on coagulometer (Stago, France). There was a highly significant relationship regarding ATIII deficiency in IUGR group in relation to control group (P value <0.001). In conclusion, we have identified antithrombin deficiency in Egyptian infants as an additional cause for low-birth weight and intrauterine growth retardation.