Association between SIRT-1 and SERPINA4 gene polymorphisms and the risk of idiopathic nephrotic syndrome among Egyptian children.

Background: Idiopathic nephrotic syndrome (INS) is the primary cause of chronic glomerular dysfunction in children. Despite extensive research, its pathophysiology remains unclear, particularly in cases that are resistant to steroids.

Aim: This research evaluated the impact of SIRT-1 (rs2273773) and SERPINA4 (rs2093266) gene variants on Egyptian children's susceptibility to INS and response to steroid therapy.

Methods and results: Genetic polymorphisms of SIRT-1 (rs2273773) and SERPINA4 (rs2093266) were screened in 135 INS children and a similar number of healthy volunteers using real-time PCR. Concerning SIRT-1 rs2273773 genotypes, the cases showed markedly greater CT, TT genotypes, and T allele incidences than the reference group, which increased the risk of INS by 2.01-, 4.03-, and 1.88-folds, respectively. Regarding SERPINA4 rs2093266 genotypes, the cases exhibited notably higher GA, AA genotypes, and the A allele frequencies than controls, which enlarged the risk of INS by 3.1-, 5.47-, and 2.82-folds, respectively. The frequency of GA and AA genotypes and the presence of the A allele of SERPINA4 rs2093266 were considerably higher in steroid-resistant versus steroid-sensitive cases. The logistic regression model stated the serum creatinine, blood urea nitrogen, and the SERPINA4 rs2093266 polymorphism as independent contributors to the risk for steroid resistance in INS cases.

Conclusion: SIRT-1 (rs2273773) and SERPINA4 (rs2093266) gene polymorphisms significantly attributed to the risk of developing INS in Egyptian children. Furthermore, the SERPINA4 (rs2093266) polymorphism has a strong correlation with steroid resistance, suggesting that it could be a target for treatment to avoid severe renal problems and adverse steroid effects.