Tarek M. Kamal

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-&agr; (−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-1RaVNTR (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.

A Study of Human Killer Cell Immunoglobulin-Like Receptor and Multidrug Resistance Gene Polymorphisms in Children With Immune Thrombocytopenia

The objective: This study was undertaken to detect characterization of the different gene polymorphisms in Human killer cell immunoglobulin-like receptor (KIR2) gene and multi-drug resistance (MDR1) gene, among childhood ITP Egyptian patients. In addition to assess the potential role of these polymorphisms in relation to types of ITP and response to different treatment modalities. Patients and Methods: A total of 48 pediatric patients with immune thrombocytopenia (ITP; 24 newly diagnosed and 24 chronic) and 35 healthy controls were investigated via polymerase chain reaction-restriction fragment length polymorphism analysis for multidrug resistance (MDR) 1 and killer cell immunoglobulin-like receptor (KIR) 2 genes. Results: The frequency of MDR1 gene in patients and control was not significant (P = .090). The CT genotype was the highest distribution among all ITP cases (62.50%, n = 30) and control (48.60%, n = 17). There was a significant difference in age at diagnosis of MDR1 gene with the CC genotype had the eldest age and lowest initial platelets count (P = .029 and P = .004). The distribution of KIR2 gene among all patients with ITP and controls was significant (P = .026) with (KIRDL2−/KIRDS2−) genotype was the most prevalent among patients. Conclusion: The frequency of MDR1 polymorphisms was not associated with susceptibility to the development and clinical progression of the disease. However, KIR2 gene polymorphisms were independently associated with childhood ITP in Egyptian patients with highest prevalence among (KIRDL2−/KIRDS2−) genotypes.

Dopamine D4 Receptor Gene Polymorphism in a Sample of Egyptian Children With Attention-Deficit Hyperactivity Disorder (ADHD):

This study aimed to detect DRD4 receptor gene polymorphisms in attention-deficit hyperactivity disorder (ADHD) children and to correlate their phenotype-genotype. Fifty children with ADHD were diagnosed by Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, criteria and were subjected to Conners Parent Rating Scale. All cases and controls were subjected to history taking, physical examination, IQ assessment, and dopamine receptor D4 (DRD4) exon 3 genotyping. The 7-repeat allele was present only in controls, whereas 2-repeat allele was present in the ADHD children (heterozygous 2-repeat allele in 16% and homozygous in 26% of cases). Eight percent of cases had homozygous 4-repeat allele vs 28% of controls, whereas 10% of cases had heterozygous 4-repeat allele vs 6% of controls, with its predominance in controls. The 2-repeat and 4-repeat alleles have been associated with more inattention, hyperactivity, and impulsivity phenotypes. In conclusion, children with ADHD had a significant presence of the 2-repeat allele and absence of the 7-repeat allele.

Assessment of glucokinase regulatory protein rs1260326 gene variant polymorphism in the development of nonalcoholic fatty liver disease among Egyptian obese children

Background Several gene variants have been identified so far by genome-wide association studies or by a candidate gene approach to be associated with fatty liver disease. Aim The aim of the present study was to assess the prevalence of rs 1260326 of the glucokinase regulatory protein (GCKR) gene in nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis among a sample of obese Egyptian children. Patients and methods This study included 100 obese children followed-up at the obesity clinic of Ain Shams University Children’s Hospital and 50 healthy, nonobese children. Study candidates were further subclassified into three groups: group I – 50 obese children with ‘no hepatomegaly’ and normal liver enzymes; group II – 30 obese children with ‘hepatomegaly’ and normal liver enzymes; group III – 20 obese children with ‘hepatomegaly and elevated liver enzymes’ (nonalcoholic steatohepatitis); and group IV – 50 healthy, nonobese children matched for age and sex as a control group only for the genetic study. Epidemiological, clinical, and laboratory data were collected from the medical records of the first three groups. The GCKR gene variant rs1260326 was studied in patients with NAFLD (groups II and III) and the control group (group IV). Results NAFLD patients (groups II and III) included 29 males and 21 females with a mean age of 8.5±4.4 years and mean duration of obesity of 4.2±2 years. There was a highly significant statistical difference between groups II, III, and I regarding duration of obesity, weight, BMI, hip circumference, waist circumference, and lipid profile. The most prevalent GCKR genotype among NAFLD was CC (52%), whereas controls showed more heterozygosity for the CT allele. The most frequently segregated allele among patients was C (69%) followed by T (31%). Conclusion The most prevalent polymorphic genotype of rs 1260326 within the GCKR among Egyptian obese children with NAFLD was CC, and the most prevalent allele among them was the C allele.