Tripathi Gaurav, Jafar Tabrez, Mandal Kaushik, Mahdi Abbas A, Awasthi Shally, Sharma Raj K, Kumar Alok, Gulati Sanjeev, Agrawal Suraksha
Department of Medical Genetics, SGPGIMS, Lucknow, India.
Indian J Med Sci. 2008 Oct;62(10):383-91.
Immunological responses may be possibly involved in the pathogenesis of idiopathic nephrotic syndrome (INS). Cytokines act as a potent immunomodulator. Pathogenesis of INS is associated with Th1 and Th2 cytokines imbalance. AIMS, SETTINGS AND DESIGN: We have investigated the association of IL-4, IL-6, and TNF-alpha gene polymorphisms and analyzed the data to evaluate the effect of these polymorphisms on the pathogenesis and clinical course of INS.
One hundred fifty children with INS were selected. Children were analyzed for IL-4, IL-6, and TNF-alpha gene polymorphisms by using polymerase chain reaction and restriction fragment length polymorphism.
Chi-square test was used for different comparisons. The synergistic effects of IL-4, IL-6, and TNF-alpha gene polymorphisms were evaluated by using logistic regression analysis.
We compared the steroid-resistant (SR) and steroid-responsive (SS) groups. Our results showed strong association of IL-6 -G174C, and IL-4 -C590T at genotypic level (P = 0.0121, OR = 14.71, 95% CI = 1.59-136.46; and P = 0.0386, OR = 7.29, 95% CI = 1.26-41.69). TNF-alpha revealed a strong association at genotypic level (P = 0.0121, OR = 14.71, 95% CI = 1.59-136.46), as well as at allelic level (P = 0.0433, OR = 2.251, 95% CI = 1.09-4.66), demonstrating that it may be considered one of the genetic risk factors affecting the steroid response in INS patients. The GG genotype of IL-6 -G174C, TT genotype of IL-4 -C590T, and AA genotype of TNF-alpha -G308A cytokine gene polymorphisms may be causative factors for nonresponsiveness towards steroid therapy among INS children.
免疫反应可能参与特发性肾病综合征（INS）的发病机制。细胞因子作为一种强大的免疫调节剂。INS的发病机制与Th1和Th2细胞因子失衡有关。目的、研究地点和设计：我们研究了白细胞介素-4（IL-4）、白细胞介素-6（IL-6）和肿瘤坏死因子-α（TNF-α）基因多态性的关联，并分析数据以评估这些多态性对INS发病机制和临床病程的影响。
选取150例INS患儿。采用聚合酶链反应和限制性片段长度多态性分析患儿的IL-4、IL-6和TNF-α基因多态性。
采用卡方检验进行不同比较。通过逻辑回归分析评估IL-4、IL-6和TNF-α基因多态性的协同作用。
我们比较了激素抵抗（SR）组和激素敏感（SS）组。我们的结果显示，在基因型水平上，IL-6 -G174C和IL-4 -C590T存在强关联（P = 0.0121，比值比[OR]=14.71，95%置信区间[CI]=1.59 - 136.46；P = 0.0386，OR = 7.29，95% CI = 1.26 - 41.69）。TNF-α在基因型水平（P = 0.0121，OR = 14.71，95% CI = 1.59 - 136.46）以及等位基因水平（P = 0.0433，OR = 2.251，95% CI = 1.09 - 4.66）均显示出强关联，表明它可能被视为影响INS患者激素反应的遗传危险因素之一。IL-6 -G174C的GG基因型、IL-4 -C590T的TT基因型以及TNF-α -G308A细胞因子基因多态性的AA基因型可能是INS患儿对激素治疗无反应的致病因素。
