title: 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.
abstract: 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.
authors.affiliation: aHematology and Oncology Unit bHuman Genetics Unit, Department of Pediatrics, Faculty of Medicine, Ain Shams University, Cairo, Egypt.
authors.forename: Galila M
authors.initials: GM
authors.lastname: Mokhtar
authors.forename: Nagham M S
authors.initials: NM
authors.lastname: El-Beblawy
authors.forename: Amira A
authors.initials: AA
authors.lastname: Adly
authors.forename: Nancy S
authors.initials: NS
authors.lastname: Elbarbary
authors.forename: Tarek M
authors.initials: TM
authors.lastname: Kamal
authors.forename: Esraa M
authors.initials: EM
authors.lastname: Hasan
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein / Q000235:genetics*; D016753:Interleukin-10 / Q000235:genetics*; D020381:Interleukin-17 / Q000235:genetics*; D015850:Interleukin-6 / Q000235:genetics*; D008297:Male; D011110:Polymorphism, Genetic; D016553:Purpura, Thrombocytopenic, Idiopathic / Q000188:drug therapy* / Q000235:genetics; D013256:Steroids / Q000627:therapeutic use*; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
chemical_list: C508609:IL10 protein, human; C440021:IL17F protein, human; C508600:IL6 protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D020381:Interleukin-17; D015850:Interleukin-6; D013256:Steroids; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10