Tieranu Ioana, Dutescu Monica I, Bara Constantin, Tieranu Cristian G, Balgradean Mihaela, Popa Olivia M
"Carol Davila" University of Medicine and Pharmacy, Bucharest, Romania.
"Prof. Dr. C. T. Nicolau" National Institute of Blood Transfusion, Bucharest, Romania.
Maedica (Bucur). 2017 Sep;12(3):164-168.
Childhood idiopathic nephrotic syndrome (INS) is one of the most common glomerular diseases, characterized by heavy proteinuria, hypoalbuminemia, dyslipidemia and generalized edema. Although some progresses were made regarding the pathogenesis of this disease, there are a lot of questions still left unanswered. Some of them involve the implications of several cytokines, including tumor necrosis factor alpha (TNF-alpha), in the development and clinical course of INS.
Our objective was to analyze the role of two single nucleotide polymorphisms of TNF-alpha gene in the development of pediatric INS and their implication in the response to corticosteroid therapy.
Seventy patients with INS and 159 healthy controls were included in this study. They were analyzed for TNF-alpha gene polymorphisms by using polymerase chain reaction. The two SNPs (rs1799724/-857C/T and rs1800629/-308G/A) were genotyped by TaqMan Genotyping Assays, association tests were performed and p values <0.05 were considered significant.
Minor alleles frequencies were 15.72% in INS patients versus 18.55% in controls for 857T allele and 11.43% in INS versus 13.2% in controls for 308A allele. Although the minor alleles were more frequent in controls than in patients, the difference was not statistically significant (p=0.46, OR=0.818 and p=0.59, OR=0.848).Analyzing the response to corticosteroid therapy, we found a low frequency of 857T allele in steroid resistant patients (9.09%) compared to steroid sensitive patients (16.95%) and controls (18.55%). Regarding 308A allele, the frequencies were 18.18% in the corticoresistant group and 10.17% in the corticosensitive one. None of them was statistically significant (p>0.05).
We conclude that neither -857C/T, nor-308G/A polymorphisms of TNF-alpha gene are associated with the susceptibility and response to steroid treatment of INS in our population. Given the small sample size used, future studies are necessary to clarify the results observed in the present study.
儿童特发性肾病综合征（INS）是最常见的肾小球疾病之一，其特征为大量蛋白尿、低白蛋白血症、血脂异常和全身性水肿。尽管在该疾病的发病机制方面取得了一些进展，但仍有许多问题未得到解答。其中一些问题涉及多种细胞因子的影响，包括肿瘤坏死因子α（TNF-α）在INS的发生发展及临床病程中的作用。
我们的目的是分析TNF-α基因的两个单核苷酸多态性在儿童INS发生中的作用及其对皮质类固醇治疗反应的影响。
本研究纳入了70例INS患者和159例健康对照。采用聚合酶链反应分析TNF-α基因多态性。通过TaqMan基因分型检测对两个单核苷酸多态性（rs1799724/-857C/T和rs1800629/-308G/A）进行基因分型，进行关联测试，p值<0.05被认为具有统计学意义。
对于857T等位基因，INS患者的次要等位基因频率为15.72%，对照为18.55%；对于308A等位基因，INS患者为11.43%，对照为13.2%。尽管对照中的次要等位基因频率高于患者，但差异无统计学意义（p = 0.46，OR = 0.818；p = 0.59，OR = 0.848）。分析对皮质类固醇治疗的反应，我们发现激素抵抗患者中857T等位基因的频率较低（9.09%），而激素敏感患者为（16.95%），对照为（18.55%）。对于308A等位基因，激素抵抗组的频率为18.18%，激素敏感组为10.17%。两者均无统计学意义（p>0.05）。
我们得出结论，在我们的研究人群中，TNF-α基因的-857C/T和-308G/A多态性均与INS对类固醇治疗的易感性和反应无关。鉴于本研究样本量较小，未来有必要进行研究以阐明本研究中观察到的结果。
