Abstract
Introduction: Steroids are the primary treatment for idiopathic nephrotic syndrome. Pharmacogenomic factors, including genetic and histological modifications, play a significant role in influencing the response to steroids. One such factor is the excessive synthesis of P-glycoprotein (permeability glycoprotein) and multidrug resistance-associated protein 1 (MDR-1), which may contribute to the development of steroid resistance and alterations in steroid pharmacokinetics.
Objectives: We examined the correlation between steroid responsiveness and the MDR-1 gene variations, specifically rs1045642 (3435T/C) and rs2032582 (2677G/T/A), in children in Iraq diagnosed with idiopathic nephrotic syndrome (INS).
Patients and Methods: In this cross-sectional study, one hundred Iraqi pediatric patients aged one to 16 years, all diagnosed with primary nephrotic syndrome and treated with prednisolone, were enrolled. After isolating genomic DNA, genotyping was performed using the allele-specific polymerase chain reaction (PCR) technique. A notable correlation was identified between the adenosine triphosphate-binding cassette B1 (ABCB1) gene SNPs 3435T>C and 2677G>T/A, and the likelihood of prednisolone resistance in these patients with nephrotic syndrome.
Results: The study included 45 cases of steroid-sensitive nephrotic syndrome (SSNS), 38 cases of steroid-dependent nephrotic syndrome (SDNS), and 17 cases of steroid-resistant nephrotic syndrome (SRNS). Our investigation revealed a significant correlation between the 3435T>C polymorphism of the ABCB1 gene and the likelihood of resistance to prednisolone in pediatric patients with nephrotic syndrome (p = 0.02). The genotype distribution for rs1045642 (3435T>C SNP) was 14 TT, 68 TC, and 18 CC. For rs2032582 (2677G/T/A SNP), the genotype distribution was 18 GG, 16 GT, 24 TT, 23 TA, and 19 AA. Additionally, the 2677G>T/A polymorphism was significantly associated with the onset of prednisolone-resistant nephrotic syndrome (P = 0.043).
Conclusion: This study concluded that children with the MDR-1 3435T/C and 2677G/T/A polymorphisms may be more vulnerable to SRNS and, therefore, may require alternative therapeutic approaches.