Mokhtar Galila M, El-Beblawy Nagham M S, Adly Amira A, Elbarbary Nancy S, Kamal Tarek M, Hasan Esraa M
aHematology and Oncology Unit bHuman Genetics Unit, Department of Pediatrics, Faculty of Medicine, Ain Shams University, Cairo, Egypt.
Blood Coagul Fibrinolysis. 2016 Apr;27(3):313-23. doi: 10.1097/MBC.0000000000000431.
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.
评估免疫性血小板减少症（ITP）患者与已知与自身免疫相关的不同细胞因子基因多态性（肿瘤坏死因子（TNF）-α、白细胞介素（IL）-10、IL-6、IL-17、IL-1Ra）之间在疾病发生、进展及对治疗反应方面的关联。通过聚合酶链反应-限制性片段长度多态性分析对50例儿科ITP患者（20例新诊断患者、30例慢性患者）及50例健康对照者进行细胞因子基因多态性研究。与对照组相比，所有患者IL-6 -174 CC基因型频率更高（P = 0.0001，比值比（OR）= 7.048，95%置信区间（CI）= 2.18 - 22.7），TNF-α（-308）的GA基因型频率更高（P = 0.001，OR = 6.469，95% CI = 2.0 - 20.9），IL-17F的CC基因型频率更高（P = 0.0001，OR = 55.545，95% CI = 14.4 - 213.2），IL-10 -1082的GG基因型频率更高（P = 0.029，OR = 3.6，95% CI = 1.08 - 12.18），IL-1Ra的A1A2基因型频率更高（P = 0.039，OR = 2.374，95% CI = 1.03 - 5.4）。与新诊断患者相比，慢性患者中IL-10 GA和IL-1Ra A1A1基因型频率更高（分别为P = 0.042，P = 0.001）。在所有ITP患者中，IL-6（-174）的GC基因型和IL-10（-1082）的GG基因型对类固醇治疗的血小板反应最佳。这表明上述细胞因子基因多态性可能与儿童ITP的易感性有关。此外，IL-10的GA基因型和IL-1Ra多态性的A1A1基因型与慢性ITP风险增加有关。IL-6（-174）和IL-10（-1082）基因可能在ITP患者类固醇治疗的有效性中发挥作用。
