Genetic Polymorphisms and Susceptibility to Parenchymal Renal Infection Among Pediatric Patients

Abstract

Patient susceptibility to bacterial urinary tract infections, which is determined by complex pathogen-host interactions, varies between individuals due to genetic variation. The neutrophil-dependent innate immune system is an important part of keeping the urinary tract sterile. This study was performed to explore single nucleotide polymorphisms (SNPs) in genes associated with neutrophil-dependent immunity in pediatric patients with severe parenchymal infections. The subjects included patients who fulfilled the diagnostic criteria of acute pyelonephritis (APN) and acute lobar nephronia (ALN) without underlying disease or structural anomalies (excluding vesicoureteral reflux). Genotyping of the genes encoding toll-like receptor 4 (TLR-4), interleukin-8 (IL-8), and IL-8 receptors CXCR1 and CXCR2 was performed by matrix-assisted laser desorption/ionization time-of-flight-based mini-sequencing analysis. A total of 17 SNPs, including missense SNPs and those located in promoter regions, were initially selected for genotyping. Only 4 SNPs with a heterozygosity rate >0.01 were evaluated further. The observed genotype frequencies satisfied Hardy-Weinberg equilibrium. Statistical analysis revealed that only IL-8 (rs4073, -251A>T) showed significant differences in genotype and allele frequency between the control and APN or ALN cases. Following the elimination of vesicoureteral reflux, which is a significant risk factor for severe parenchymal infection, a single SNP in IL-8 (rs4073) was found to be associated with clinically severe ALN. The AA genotype and A allele of the IL-8 SNP is related to patient susceptibility to parenchymal infection and is correlated with the severity of infection in pediatric APN and ALN patients, probably due to the upregulation of IL-8 expression.