Interleukin-1 Receptor Antagonist Gene Polymorphisms in Egyptian Children and Adolescents With Primary Immune Thrombocytopenia: Association With Disease Susceptibility, Response to Therapy, and Outcome.

Immune thrombocytopenia (ITP) is one of the most common hematologic disorders with poorly predictable clinical course and outcome. We studied the distribution of interleukin 1 receptor antagonist (IL-1Ra) gene polymorphism (intron-2) among children and adolescents with ITP and correlated IL-1Ra gene polymorphism to disease susceptibility, response to therapy, and outcome. Sixty children with ITP (mean age: 9.2±4.5 y) and 100 healthy controls (mean age: 8.83±4.05 y) were enrolled. The frequencies of the allele A2 and genotype A1A2 were significantly higher in patients compared with controls ( P <0.0001, P =0.0008, respectively). Allele A2 conferred 3.1 times increased relative risk for disease development. Allele A2 and genotypes A1A2 and A2A2 were significantly more frequent among remitted patients ( P =0.028 and 0.024, respectively). There was no significant difference between different genotypes and alleles regarding bleeding score ( P >0.05). Patients with polymorphic allele A2 (A1A2/A2A2) showed significantly better response to steroids than those with homozygous wild allele A1 ( P =0.028). IL-1Ra polymorphism might contribute to the susceptibility to ITP in Egyptian children. The presence of A2 polymorphic allele of IL-1Ra gene was found to be associated with better disease outcome and response to steroids than those with homozygous wild allele.

Klf10 Gene, a Secondary Modifier and a Pharmacogenomic Biomarker of Hydroxyurea Treatment Among Patients With Hemoglobinopathies.

BACKGROUND: The klf10 gene could indirectly modify γ-globin chain production and hence the level of fetal hemoglobin (HbF) ameliorating the phenotype of ß-hemoglobinopathies and the response to hydroxycarbamide (hydroxyurea [HU]) therapy. In this study, we aimed to evaluate the frequency of different genotypes for the klf10 gene in ß-thalassemia major (B-TM), ß-thalassemia intermedia (B-TI), and sickle cell disease (SCD) patients by polymerase chain reaction and to assess its relation to disease phenotypes and HU response. METHODS: This cross-sectional study included 75 patients: 50 B-TM, 12 SCD, and 13 B-TI patients (on stable HU dose). The relation of the klf10 gene polymorphism (TIEG, TIEG1, EGRα) (rs3191333: c*0.141C>T) to phenotype was studied through baseline mean corpuscular volume, HbF, and transfusion history, whereas evaluation of response to HU therapy was carried out clinically and laboratory. RESULTS: The frequency of the mutant klf10 genotype (TT) and that of the mutant allele (T) was significantly higher among B-TM patients compared with those with B-TI and SCD patients. Only homozygous SCD patients for the wild-type allele within the klf10 gene had a significantly lower transfusion frequency. The percentage of HU responders and nonresponders between different klf10 polymorphic genotypes among B-TI or SCD patients was comparable. CONCLUSIONS: Although the klf10 gene does not play a standalone role as an HbF modifier, our data support its importance in ameliorating phenotype among ß-hemoglobinopathies.

Screening of Egyptian obese children and adolescents for insertion/deletion (I/D) polymorphism in angiotensin-converting enzyme gene.

BACKGROUND: /aims: The role of angiotensin-converting enzyme (ACE) gene polymorphism in the development of obesity and hypertension in children has not been widely studied. We aimed to screen Egyptian obese children and adolescents for insertion/deletion (I/D) polymorphism in the ACE gene. METHODS: One hundred forty-two children and adolescents were included (70 with simple obesity and 72 controls). Blood pressure was measured, and anthropometric parameters were assessed in all included children and adolescents. Fasting lipid profile, fasting glucose, and insulin were measured. DNA extraction and ACE I/D polymorphism genotyping were also performed. RESULTS: Obese children had a higher frequency of DD genotype (30% in obese versus 11.1% in controls, P = .01) and D alleles (61.8% in obese versus 48.6% in controls, P = .01). Obese children with hypertension and prehypertension had higher frequency of DD genotype than II genotype and higher D alleles than I alleles. DD genotype and D allele were independently associated with hypertension (OR: 9.86 and 11.57, respectively, P < .001), while dyslipidemia and insulin resistance were not associated with the ACE I/D gene polymorphism. CONCLUSION: DD genotype and D-allele of the ACE gene polymorphism were associated with obesity and with hypertension and pre-hypertension in Egyptian children.

Cytokine gene polymorphism [tumor necrosis factor-alpha (-308), IL-10 (-1082), IL-6 (-174), IL-17F, 1RaVNTR] in pediatric patients with primary immune thrombocytopenia and response to different treatment modalities.

To evaluate the association between development, progression, and response to therapy among patients with immune thrombocytopenia (ITP) and different cytokine gene polymorphisms known to be related to autoimmunity [tumor necrosis factor (TNF)-alpha, interleukin (IL)-10, IL-6, IL-17, IL-1Ra]. A total of 50 pediatric patients with ITP (20 newly diagnosed, 30 chronic) and 50 healthy controls were investigated via PCR-restriction fragment length polymorphism analysis for cytokine gene polymorphism. Compared with controls, all patients showed a higher frequency of IL-6-174 CC [P = 0.0001, odds ratio (OR) = 7.048, 95% confidence interval (CI) = 2.18-22.7], higher GA genotype of TNF-α (-308) (P = 0.001, OR = 6.469, 95% CI = 2.0-20.9), higher CC genotype of IL-17F (P = 0.0001, OR = 55.545, 95% CI = 14.4-213.2), higher GG of IL-10-1082 (P = 0.029, OR = 3.6, 95% CI = 1.08-12.18), and A1A2 genotype of IL-1Ra (P = 0.039, OR = 2.374, 95% CI = 1.03-5.4). IL-10 GA and IL-1Ra A1A1 genotypes were higher among chronic patients (P = 0.042, P = 0.001 respectively) compared with newly diagnosed ones. Best platelet response to steroid treatment was found among GC genotype of IL-6 (-174) and GG genotype of IL-10 (-1082) in all patients with ITP. This suggests that previously mentioned cytokine gene polymorphisms possibly contribute to the susceptibility of acquisition of childhood ITP. Furthermore, GA genotype of IL-10 and A1A1 genotype of IL-1Ra polymorphisms are associated with increased risk of chronic ITP. IL-6 (-174) and IL-10 (-1082) genes might play a role in the effectiveness of steroid therapy among patients with ITP.