Impact of tumor necrosis factor-alpha gene variant in pediatric nephrotic syndrome: a meta-analysis

TL;DR

This study finds that a specific gene variant may increase the risk of childhood nephrotic syndrome, but results are limited by small sample size and high variability.

Contribution

A meta-analysis linking the TNFα-308 G/A gene polymorphism to childhood nephrotic syndrome risk.

Findings

The TNFα-308 A allele is significantly associated with increased risk of childhood nephrotic syndrome.

High heterogeneity (I²=80%) and limited ethnic diversity reduce the robustness of the findings.

Significant associations were found in co-dominant and recessive genetic models.

Abstract

This study aims to explore the risk associated with the Tumour Necrosis Factor-Alpha (TNFα)-308 G/A (rs1800629) gene polymorphism in relation to Childhood Nephrotic Syndrome (NS). The primary goal of the meta-analysis was to investigate the relationship between Nephrotic Syndrome and the TNFα 308 G/A [rs1800629] polymorphism of the cytokine gene. We conducted a systematic search across electronic databases like PubMed and Google Scholar to collect data from five distinct case-control studies focused on the TNFα 308 G/A gene variant, covering the period from 2010 to 2022. By aggregating allele and genotype frequencies from these studies, we computed the 95% confidence interval of odds ratio [OR] to assess the strength of the association. To evaluate heterogeneity and potential publication bias in the selected studies, Stats Direct software was employed. The sample size encompassed 1,560 individuals, including 628 cases and 932 controls from five separate case-control studies. The TNFα allele-A displayed significant heterogeneity [I²=80%, 95% CI] when compared to the G allele, and a statistically significant pooled OR of 2.32 [P = 0.0056*] was observed. In the overall analysis, no significance association was found in the dominant model [P = 0.068], but a significant association was detected in the recessive model [P = 0.0096*]. Consistent findings were observed in the co-dominant model, where both AA vs. GG [P = 0.0075*] and GA vs. GG [P = 0.0219*] showed significant associations. These results suggest a potential increase in the risk of the disease associated with the polymorphism of TNFα 308 G/A. The small number of studies, high heterogeneity (I² = 80%), and limited ethnic diversity may affect the robustness and generalizability of findings. Additionally, language bias and lack of confounder adjustment limit interpretability. The TNFα 308 G/A polymorphism was identified as being associated with the risk of developing childhood NS.

Registration: Registered in PROSPERO with ID: CRD420251083425.

The online version contains supplementary material available at 10.1038/s41598-025-15387-w.

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