Associations of TNF-α, IL-2 and IL-10 gene polymorphisms in children with primary nephrotic syndrome

Childhood nephrotic syndrome (NS), is a glomerular disease, characterized by heavy proteinuria, hypoalbuminemia, hyperlipidemia, and edema. The pathophysiology of primary NS suggests a strong connection between genetic susceptibilities and inflammatory processes. This study investigated the association between TNF-α (G238A, G308A), IL-2 (T330G), and IL-10 (A592C) gene polymorphisms and susceptibility to steroid-sensitive nephrotic syndrome (SSNS) and steroid-resistant nephrotic syndrome (SRNS).

A total of 300 samples from 100 SSNS and 100 SRNS patients, as well as 100 healthy controls aged between 1 and 18 years, were genotyped using the restriction fragment length polymorphism (RFLP) method. Genotype frequencies were analyzed and compared using odds ratios (ORs) and confidence intervals (CIs) to assess disease association.

In SSNS, TNF-α G238A (AA), TNF-α G308A (GA and AA), and IL-2 T330G (TG) were associated with increased disease risk, whereas IL-10 A592C (CC) showed a protective effect. In SRNS, TNF-α G238A and G308A (AA and GA), IL-2 T330G(TG) and IL-10 A592C (AC and CC) were significantly associated with increased risk, with the strongest effect observed for the GA genotype of TNF-α G308A. Comparative analysis between SSNS and SRNS indicated stronger associations of TNF-α G308A and IL-10 A592C with SRNS. After Bonferroni correction, only these polymorphisms remained significantly associated.

Genetic polymorphisms in TNF-α G308A and IL-10 A592C may contribute to susceptibility to SRNS, highlighting the role of inflammatory pathways in disease pathogenesis. These findings may support the identification of potential biomarkers for disease susceptibility and immune dysregulation in pediatric NS.