Does cytokine gene polymorphism affect steroid responses in idiopathic nephrotic syndrome?

Abstract

Background: 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-α gene polymorphisms and analyzed the data to evaluate the effect of these polymorphisms on the pathogenesis and clinical course of INS. Materials and Methods: One hundred fifty children with INS were selected. Children were analyzed for IL-4, IL-6, and TNF-α gene polymorphisms by using polymerase chain reaction and restriction fragment length polymorphism. Statistical Analysis Used: Chi-square test was used for different comparisons. The synergistic effects of IL-4, IL-6, and TNF-α gene polymorphisms were evaluated by using logistic regression analysis. Results and Conclusions: 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-α 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-α -G308A cytokine gene polymorphisms may be causative factors for nonresponsiveness towards steroid therapy among INS children.