Association of the rs1128503 and rs1045642 polymorphisms in the MDR-1 gene with steroid responsiveness in Iraqi children with idiopathic nephrotic syndrome

Abstract

Steroid-resistant nephrotic syndrome (SRNS) is a leading cause of end-stage renal disease in children, with an increasing number of cases. Polymorphisms in the MDR-1 gene were reported to contribute to SRNS development, but with varying results among different ethnicities. Thus, we investigated the association of the MDR-1 rs1128503 (C1236T) and rs1045642 (C3435T) polymorphisms with steroid responsiveness in Iraqi children with idiopathic nephrotic syndrome (INS). This case-control study was conducted at the Babylon Hospital for Maternity and Pediatrics. Children with SRNS (n=32) and steroid-sensitive nephrotic syndrome (SSNS; n=32) were genotyped via the polymerase chain reaction-restriction fragment length polymorphism. The genotypes were subjected to association testing and haplotype analysis. The C1236T TT genotype was associated with a higher risk of developing SRNS compared to the CC and TC genotypes (odds ratio [OR]=10.33, 95% confidence interval [95% CI]=1.208-88.362; p -value=0.026; recessive model). The combination of the two TT genotypes of C1236T and C3435T variants was significantly more frequent ( p -value=0.029) in SRNS (88.9%) than in SSNS (11.1%). The haplotype analysis showed no association between the C1236T and C3435T haplotypes and steroid responsiveness, but the TC haplotype was associated with an age at onset of ≥8 years ( p -value=0.0028). In conclusion, this study revealed that children who have the MRD-1 C1236T TT genotype alone or combined with the C3435T TT genotype may be at increased risk of developing SRNS and in need of other therapeutic strategies. Additional research is required to identify other genetic contributions to steroid responsiveness and further understand their