Genetic Polymorphisms and Susceptibility to Parenchymal Renal Infection Among Pediatric Patients

Cheng, Chi-Hui; Lee, Yun Shien; Tsau, Yong-Kwei; Lin, Tzou Yien

doi:10.1097/inf.0b013e3181ff84ff

Cited by 30 publications

(35 citation statements)

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“…Previous studies have shown that single nucleotide polymorphisms (SNPs) in the TLR-2 and TLR-4 genes can affect host susceptibility to UTIs [7], [11], [13], [16]–[19]. In contrast, we did not observe this association for TLR-4 in APN and ALN [12].…”

Section: Introductioncontrasting

confidence: 99%

Genetic Polymorphisms in Toll-Like Receptors among Pediatric Patients with Renal Parenchymal Infections of Different Clinical Severities

et al. 2013

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BackgroundAlthough several studies have suggested single gene defects or variations in the genes associated with host immune response could confer differences in susceptibility to urinary pathogen invasion, no studies have examined the genetic polymorphisms in various toll-like receptors (TLRs) that activate innate immune responses in pediatric renal parenchymal infections of different clinical severities, namely acute pyelonephritis and the clinically more severe disease, acute lobar nephronia.MethodologyPatients who fulfilled the diagnostic criteria for acute pyelonephritis (APN) and acute lobar nephronia (ALN) without underlying diseases or structural anomalies, except for vesicoureteral reflux (VUR), were enrolled. Genotyping of the single nucleotide polymorphisms (SNPs) in the genes encoding TLR-1, TLR-2, TLR-4, TLR-5, and TLR-6 was performed by matrix-assisted laser desorption/ionization time-of-flight-based mini-sequencing analysis.Principal FindingsA total of 16 SNPs were selected for genotyping. Analysis of 96 normal and 48 patients’ samples revealed that only four SNPs had heterozygosity rates >0.01. These SNPs were selected for further investigation. Hardy-Weinberg equilibrium was satisfied for the observed genotype frequencies. Statistically significant differences in the genotype frequency of TLR-2 (rs3804100, T1350C) between controls and ALN or (APN+ALN) combined group were identified using the recessive model with the correction for multiple-SNP testing. Further genotype pattern frequency analysis in TLR-2 SNPs (rs3804099 and rs3804100) showed significantly reduced occurrence of the rare allele homozygote (CC+CC) in the no-VUR subgroup of APN and ALN cases.ConclusionsAs the inflammatory responses in ALN patients are more severe than those in APN patients (higher CRP levels, longer duration of fever after antibiotic treatment), these findings suggest that the genetic variant in TLR-2 (rs3804100, T1350C) may protect the host from severe urinary tract infections as ALN.

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Section: Introductioncontrasting

confidence: 99%

Genetic Polymorphisms in Toll-Like Receptors among Pediatric Patients with Renal Parenchymal Infections of Different Clinical Severities

et al. 2013

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“…Several studies have linked individual susceptibility to uropathogens to defects in the genes that modulate innate immune responses to bacterial clearance and elimination. Genotyping of the promoter regions and genes encoding Toll-like receptor-4 (TLR-4), IL-8, and IL-8 receptors CXCR1 and CXCR2 in children with UTI found that the AA genotype and A allele of the IL-8 single-nucleotide polymorphism (SNP) was related to susceptibility to and severity of upper UTI [15 ▪ ]. …”

Section: Pathogenesis Of Urinary Tract Infectionmentioning

confidence: 99%

Update on recent guidelines for the management of urinary tract infections in children

Paintsil

2013

Current Opinion in Pediatrics

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Purpose of review Recent guidelines on the management of urinary tract infections (UTIs) in children have seen a shift from aggressive imaging studies and the use of prophylactic antibiotics to a more restrictive and targeted approach. This review focuses on new additions to the literature on management of UTI from January 2011 to September 2012. Recent findings The causal relationship between UTI–vesicoureteral reflux (VUR) and renal scarring has been challenged by several studies. Concerns about unnecessary exposure to ionizing radiation, invasiveness of some of the procedures, and risk of infection have also been raised. With improved prenatal ultrasound, a ‘top-down’ approach to investigating febrile UTI in children using renal bladder ultrasound alone as an initial study has become popular. Several studies have reported that prophylactic antibiotics and imaging studies after first UTI can be reduced substantially without affecting the risk of recurrent UTI or renal scarring. Summary The use of targeted imaging approach in evaluating febrile UTI in children may lead to improved resource use and reduction of potential harmful procedures and interventions, without affecting outcomes of UTI in children. Providers using current guidelines should endeavor to collect practice-based evidence to validate and inform future guidelines.

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“…Researches have revealed that the two polymorphisms are associated with different diseases such as gastric cancer, pyelonephritis, hepatitis C virus-induced hepatocellular carcinoma, etc. [16][17][18]. Previously, we have reported that the TLR4 +3725G/C polymorphism is associated with an increased risk of bladder cancer [19].…”

Section: Introductionmentioning

confidence: 97%

Toll-like receptor 4 gene polymorphism downregulates gene expression and involves in susceptibility to bladder cancer

Shen

Bu²,

Zhang

et al. 2014

Tumor Biol.

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Bladder cancer is the ninth most frequent malignancy in China. Toll-like receptor 4 (TLR4) is expressed on various cells and greatly involves in immune responses. Genetic polymorphism may affect the pathogenesis of diseases through various pathways. In the current study, we evaluated the association between genetic polymorphisms in TLR4 and risk of bladder cancer. We also examined the effect of the polymorphisms on gene expression. The TLR4 -729G/C and -260G/C polymorphisms were genotyped in 282 bladder cancer patients and 298 healthy controls in the Chinese population. Results showed that subjects with -729GC genotype are at significantly higher risk of bladder cancer than those with GG genotype [odds ratio (OR) = 2.50, 95% confidence interval (CI) = 1.39-4.48, P = 0.002]. Similarly, TLR4 -729C allele revealed a positive association with the disease (OR = 2.39, P = 0.002). The other polymorphism, TLR4 -260G/C, did not present clear correlations with bladder cancer. To understand the function of the polymorphisms, we evaluated TLR4 messenger RNA (mRNA) and protein levels in CD4+ T cells, CD8+ T cells, and monocytes from subjects carrying different TLR4 genotypes. Results revealed that subjects carrying -729GC genotype had significantly downregulated mRNA and protein levels of TLR4 in CD4+ T cells, CD8+ T cells, and monocytes compared to those carrying GG genotype. However, subjects with -260G/C polymorphism did not show any differences in gene expression from immune cells These data suggest that TLR4 polymorphism is associated with increased susceptibility to bladder cancer possibly by downregulating gene expression in various immune cells.

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Genetic Polymorphisms and Susceptibility to Parenchymal Renal Infection Among Pediatric Patients

Abstract: 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.

Cited by 30 publications

References 30 publications

Genetic Polymorphisms in Toll-Like Receptors among Pediatric Patients with Renal Parenchymal Infections of Different Clinical Severities

Genetic Polymorphisms in Toll-Like Receptors among Pediatric Patients with Renal Parenchymal Infections of Different Clinical Severities

Update on recent guidelines for the management of urinary tract infections in children

Toll-like receptor 4 gene polymorphism downregulates gene expression and involves in susceptibility to bladder cancer

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