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Preliminary study regarding the association between tumor necrosis factor alpha gene polymorphisms and childhood idiopathic nephrotic syndrome in Romanian pediatric patients
Background: 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.
Objective: 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.
Material and methods: 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.
Results: Minor alleles frequencies were 15.72% in INS patients versus 18.55% in controls for 857*T allele and 11.43% in INS versus 13.2% in controls for 308*A 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 857*T allele in steroid resistant patients (9.09%) compared to steroid sensitive patients (16.95%) and controls (18.55%). Regarding 308*A 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).
Conclusions: 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.
Keywords: nephrotic syndrome, TNF-alpha polymorphisms, steroid response