Genetic Susceptibility to Glomerulonephritis in Children: Analysis of Structural Kidney Genes and Immune System Genes

Abstract

Background/Objectives: Glomerulonephritis (GNs) is a heterogeneous group of inflammatory kidney diseases. Novel genetic methods have revealed some disease-causing and susceptibility genes underlying primary and secondary GNs. We aimed to investigate the presence of the single nucleotide polymorphisms (SNPs) rs12917707, found in the UMOD gene, and rs17319721, found in the SHROOM3 gene, as well as different polymorphisms in immune system genes in a group of children with GN. Method: The study included 71 children with GN (40 with primary and 31 with secondary GN) and 119 healthy children (HC). SNPs of the UMOD (rs12917707), SHROOM3 (rs17319721), IL10 (rs1800871 and rs3024505), IL6 (rs1800795), IL12B (rs3212227), IL23R (rs11209026 and rs1800896), and TNF (rs361525 and rs1800629) genes were genotyped. Results: The median age of the patients was 8 years at the onset of GN and 14 years at sampling. Allele A for rs1800629 in the TNF gene was more common in patients with GN in comparison to HCs (p = 0.009), followed by the difference in genotype distributions (p = 0.021), where AA and GA genotypes were more prevalent in patients. We found a statistically significant difference in haplotype distributions between patients and HCs for TNF, with GN patients having the GGAG haplotype more frequently and HCs having GGGG (p < 0.05). No correlation between the investigated SNPs and patient clinical characteristics (disease onset, primary or secondary GN, severity of disease, occurrence of remission, and presence of hypertension) was observed. Conclusions: An association between the TNF gene and different types of GN was noticed in children with GN. This may help us to understand the pathogenesis of these disorders and develop new treatments to cover the unmet needs of children with GN.

Keywords: TNF gene; cytokines; glomerulonephritis; single nucleotide polymorphism; tumor necrosis factor.