Impact of Genotype of Beta Globin Gene on Hepatic and Myocardial Iron Content in Egyptian Patients with Beta Thalassemia.

Iron overload causes most of the mortality and morbidity associated with thalassemia. Excess iron deposits primarily in the liver, but once a threshold level is reached, iron loading may occur in other tissues such as the heart. Magnetic resonance imaging is a well established technique to noninvasively quantify myocardial and liver iron content. More than 300 disease-causing mutations have been identified. We aimed to determine the impact of genotype on liver iron content in patients with beta thalassemia. Cross sectional study was carried on 73 patients with beta thalassemia. MRI liver and heart was performed to determine hepatic and myocardial iron overload. Genotyping was determined by DNA sequencing technique. The mean liver iron content was 17.4 mg/g dw and mean cardiac T2* was 25.5 ms in our patients. Patients with ß0ß0 were associated with significantly higher liver and myocardial iron content compared to those with ß0ß+ and ß+ß+ genotypes. There was a clear association between genotype and both hepatic and myocardial iron overload. Patients with ß0ß0 had significantly higher liver and heart iron content compared to those with ß0ß+ and ß+ß+ genotypes. Liver iron content was strongly correlated to serum ferritin levels and myocardial iron overload.

Serum and CSF adiponectin, leptin, and interleukin 6 levels as adipocytokines in Egyptian children with febrile seizures: a cross-sectional study.

BACKGROUND: A febrile seizure (FS) is the most common convulsive disorder in children. Activation of cytokine network is involved in FS pathogenesis. Adiponectin, leptin and IL-6 are the major adipocytokines secreted by fat cells. To date, only a few studies concerned the association of adipocytokines with febrile seizures. In this study, we tried to investigate serum and CSF levels of adiponectin, leptin, and interleukin-6 (IL-6); as adipocytokines, for the first time in Egyptian children with febrile seizures. METHODS: This was a prospective cross-sectional study included one hundred patients with febrile seizure, and matched with age, gender, 100 children with febrile illness without seizures (febrile control, FC) and 100 healthy control group (HC). Serum and cerebrospinal fluid (CSF) levels of adiponectin, leptin, and (IL-6) were measured by enzyme-linked immunosorbent assay (ELISA) method. RESULTS: Serum adiponectin was significantly higher in children with FS (16.8 ± 3.7 ug/ml) and the FC group (18.3 ± 4.3 ug/ml) compared to the HC group (9.5 ± 2.2 ug/ml); P < 0.05, respectively. Serum leptin was significantly lower in children with FS (0.9 ± 0.3 ng/ml) compared to both the FC group (4.7 ± 1.2 ng/ml) and the HC group (1.8 ± 0.4 ng/ml); P < 0.01, respectively. Children with FS had significantly higher serum IL-6 levels (43.7 ± 11.7 ng/ml) than the FC group (21.9 ± 4.5 ng/ml) and the HC group (6.5 ± 1.8 ng/ml); P < 0.01, respectively. Patients with simple febrile seizures (SFS) had serum and CSF adiponectin levels similar to those with complex febrile seizures (CFS); (P > 0.05). Serum and CSF leptin levels were significantly lower in patients with CFS compared to the SFS group (P < 0.05). Serum and CSF IL-6 levels were significantly higher in patients with CFS compared to the SFS group (P < 0.01). On multivariate logistic regression analysis, the high serum IL-6 levels was the most significant risk factor associated with febrile seizures among studied children (OR: 6.2; 95 % CI: 3.58 -10.57; P = 0.0001). CONCLUSION: Our data brought a novel observation that some adipocytokines like leptin and IL-6 could be, at least in part, an aetiopathogenetic factor in the manifestation of febrile seizures in susceptible Egyptian children. Moreover, we observed a significant association between high CSF IL-6 levels and susceptibility to complex febrile seizures as did the low CSF leptin levels.

Interleukin-6 gene polymorphisms in Egyptian children with febrile seizures: a case-control study.

BACKGROUND: Febrile seizures are the most common form of childhood seizures. Among pro-inflammatory cytokines, interleukin-6 is the key acute-phase cytokine. To date, only a few studies concerned the association of interleukin-6 gene polymorphisms with febrile seizures.In this study, we aimed to investigate 3 cytokine single-nucleotide polymorphisms situated at positions -174 (G/C), -572 (G/C), and -597 (G/A) in the promoter region of the interleukin-6 gene for the first time in Egyptian children with febrile seizures. METHODS: This was a case-control study included 100 patients with febrile seizure, and matched with age, gender, ethnicity 100 healthy control subjects. Interleukin-6 -174 (G/C), -572 (G/C), and -597 (G/A) polymorphisms were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), while the serum IL6 levels were measured by ELISA method. RESULTS: Compared to the controls subjects, the frequency of the -174 GG and -597 GG IL6 genotypes were observed to be increased in children with febrile seizures (OR: 4.17; 95 % CI: 1.86-9.49; P <0.01 and OR: 1.96; 95 % CI: 1.06-3.63;P <0.05, respectively). We found a significant positive association between the -597 GG genotype and susceptibility to complex febrile seizures as did the G allele at the same position (OR: 4.2; 95 % CI: 1.4-13.3 for the GG genotype; P <0.01) and (OR: 2.89; 95 % CI: 1.1-7.7 for the G allele; P <0.05 respectively). Our data revealed no association between IL6- genotypes and serum IL6 levels in patients with febrile seizures (P > 0.05). CONCLUSION: In conclusion, our data brought a novel observation that the presence of a G allele or GG genotype at the -174 and the GG genotype at the -597 positions of the promoter region of the interleukin-6 gene constitute risk factors for developing febrile seizures in Egyptian children. Moreover, we observed a significant positive association between the IL6 -597 GG genotype and susceptibility to complex febrile seizures as did the G allele at the same position. However, we found no association between IL6- genotypes and serum IL6 levels in patients with febrile seizures.

Serum Hepcidin Levels in Childhood-Onset Ischemic Stroke: A Case-Control Study.

Recently, hepcidin, an antimicrobial-like peptide hormone, has evolved as the master regulator of iron homeostasis. Despite the growing evidence of iron imbalance in childhood-onset ischemic stroke, serum hepcidin level in those patients has not yet been researched. In this study, we aimed to estimate serum (hepcidin) level in acute ischemic stroke (AIS) patients and to investigate whether subcutaneous enoxaparin sodium, which is a low-molecular-weight heparin (LMWH) derivative, could modulate serum hepcidin level in those patients. This was a case-control study included 60 (AIS) cases, and 100 healthy children with comparable age and gender as control group. For all subjects' serum hepcidin, interleukin-6 (IL-6), and soluble transferrin receptor [sTfR]) levels were assessed by (enzyme-linked immunosorbent assay [ELISA] method). Iron parameters including (serum iron, ferritin, transferrin, and total iron binding capacity [TIBC]) were also measured. The patients were subdivided according to treatment with an LMWH derivative into 2 groups and serum hepcidin levels were assessed initially and 1 week after stroke onset for all cases. We found that AIS cases had higher serum iron, ferritin, and IL6 levels compared to the control group (all P < 0.01). Serum hepcidin was significantly higher in AIS cases (median, 36[15-73]ng/mL) compared to the control group (median, 24[10-41]ng/mL; P < 0.01). On the 1st day of AIS diagnosis, serum hepcidin levels were similar in both stroke subgroups (P > 0.05). However, on the 7th day of diagnosis serum hepcidin level decreased significantly in AIS cases treated with LMWH (group 1) (median, 36 vs 21 ng/mL; P < 0.01, respectively). Meanwhile, no significant change was observed in serum hepcidin level in AIS cases not treated with LMWH (group 2) (P > 0.05). Serum hepcidin showed significant positive correlations with serum iron, transferrin saturation, ferritin, and IL6 (r = 0.375, P < 0.05; r = 0.453, P < 0.05; r = 0.687, P < 0.01; r = 0.515, P < 0.01; respectively). Our data brought a novel observation of elevated serum hepcidin level in pediatric AIS patients and pointed out that treatment with LMWH could modulate hepcidin level in those patients.