تأثير التعدد الجيني لناقل ABCB1 على فعالية علاج البريدنيزولون لدى المرضى العراقيين المصابين بالمتلازمة الكلوية

Effects of Genetic Polymorphism of ABCB1 Transporter on Prednisolone Efficacy in Iraqi Nephrotic Syndrome Patients

Abstract
Nephrotic syndrome is a common pediatric kidney disorder characterized by excessive protein loss in the urine due to increased glomerular permeability. It typically presents with proteinuria, hypoalbuminemia, generalized edema, and hypercholesterolemia. While several underlying causes have been identified, the exact mechanisms of idiopathic nephrotic syndrome remain unclear. Previous studies have explored the potential role of ABCB1 gene polymorphisms in steroid resistance among affected patients, but the results have been inconclusive. This study aims to investigate the association between the ABCB1 gene polymorphisms 3435T>C (rs1045642) and 2677G>T/A (rs2032582) and susceptibility to prednisolone resistance in children with nephrotic syndrome in Iraq.
Methodology: In this cross-sectional study, a total of 100 Iraqi pediatric patients, aged between 1 and 16 years, diagnosed with primary nephrotic syndrome and undergoing prednisolone therapy, were enrolled. Biochemical parameters (serum albumin, serum cholesterol, serum creatinine, blood urea and urine protein) were assessed. Genomic DNA was isolated, and genotyping was conducted using the allele-specific polymerase chain reaction (AS-PCR) technique.
Results: This study demonstrated a significant association between the 3435T>C polymorphism (rs1045642) of the ABCB1 gene and prednisolone resistance in pediatric patients with nephrotic syndrome (p = 0.02). The genotype distribution for rs1045642 was TT: 14%, TC: 68%, and CC: 18%. Steroid-dependent nephrotic syndrome was more common among individuals with the TC genotype.
For the rs2032582 polymorphism (2677G>T/A), the genotype distribution was GG: 18%, GT: 16%, TT: 24%, TA: 23%, and AA: 19%. Steroid-dependent nephrotic syndrome was most prevalent in individuals with the GT genotype, whereas steroid-resistant cases were most commonly associated with the AA genotype. A significant association was found between the 2677G>T/A polymorphism and an increased risk of prednisolone-resistant nephrotic syndrome (p = 0.043).
Conclusion: This study demonstrates that the 3435T>C and 2677G>T/A polymorphisms in the ABCB1 gene are associated with an increased risk of prednisolone resistance in Iraqi children with nephrotic syndrome. These findings suggest that genetic testing for ABCB1 polymorphisms may have potential in predicting steroid responsiveness in pediatric nephrotic syndrome patients. However, further research is needed to validate these associations and to support the development of evidence-based guidelines for their application in clinical practice.