Association of the MDR1 Variants (rs2032582 and rs2032583) with Steroid Response in Iraqi Children with Idiopathic Nephrotic Syndrome

Abstract

Background: Several studies linked the development of steroid-resistant nephrotic syndrome (SRNS) to genetic variations in the multidrug resistance 1 (MDR1) gene, though a disparity in findings was underlined among children with different ethnic origins. Objective: This study examined the relationship between MDR1 variants (rs2032582 and rs2032583) and the risk of developing SRNS in Iraqi patients with idiopathic nephrotic syndrome (INS). Methods: This case-control study included children with steroid-sensitive INS (SSNS; n=30) and SRNS (n=30) from the Babylon Hospital for Maternity and Pediatrics. Sanger sequencing was used to determine the participants’ genotypes. Results: The rs2032582 genotypes and alleles were not associated with SRNS development risk. It was also found that kids who had both the wild or mutant homozygous genotypes for rs2032583 and rs2032582 variants were more likely to get SRNS [OR (95%CI):30.18 (1.55–588.5), p=0.008] than kids who had both the heterozygous genotypes for rs2032583 and either genotype of rs2032582. Conclusions: Nephrotic children who have homozygous genotypes (wild or mutant) for the rs2032583 and rs2032582 variants likely resist prednisolone therapy, and an alternative therapeutic regimen may be warranted. Further investigations are needed to elucidate the potential implications of MDR1 variants for personalizing drug therapy in INS children.