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

Abstract

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.