Association of cytokine genes polymorphisms and the response to corticosteroid therapy in children with idiopathic nephrotic syndrome: A pilot study in Egypt

Abstract

The pathogenesis of idiopathic nephrotic syndrome (INS) is associated with Th1 and Th2 cytokines imbalance. Cytokines act as mediators of inflammation in childhood NS. The objectives are to investigate the role of cytokine genes polymorphisms (IL6-G174C, IL4-C590T, and TNFα-G308A and the response to corticosteroid therapy in children with INS in Egypt. 90 children were included in this study, they divided into 3 groups: 30 children with steroid sensitive nephrotic syndrome (SSNS), 30 children with steroid resistant nephrotic syndrome (SRNS) and 30 age and sex matched healthy control children. Polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) were used to assess IL6-G174C, IL4-C590T, and TNFα-G308A polymorphisms. A significant association was found between the CC genotype and the C allele in IL6-G174C and INS group when compared to the control group (P = 0.003 and 0.009, OR = 4.3 and 2.67 respectively), also, they were significantly associated with SRNS compared to SSNS groups (P = 0.008 and 0.000, OR = 4.93 and 5.82 respectively). Also, TNF-α G308A AA genotype A allele were significantly associated with INS group compared to the control group (P = 0.045 and 0.014, OR = 3.5 and 3.51 respectively) and on comparing SRNS to SSNS groups TNF-α G308A A allele was only significantly associated with SSNS group (p = 0.032, OR = 2.83). IL4-C590T showed no significant difference in the genotypes or the allele distribution between the studied groups. In conclusion, IL6-G174C and TNFα-G308A polymorphisms may affect response to steroid therapy in childhood INS.

Keywords: Idiopathic nephrotic syndromes, IL-4, IL-6, TNF-α gene polymorphism, steroid response.