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Investigation of TLR4 Polymorphism in Children with Vesicoureteral Reflux and Renal Scarring

N M Sav1, R Eroz2, Duran N Kalay3

  • 1Department of Pediatric Nephrology, Duzce University, Duzce, Turkey.

Balkan Journal of Medical Genetics : BJMG
|March 12, 2025
PubMed

Insights

Toll-like receptor 4 (TLR4) gene variations are linked to kidney scarring in children with vesicoureteral reflux (VUR). Specific TLR4 polymorphisms were more common in children with scarring, suggesting a genetic role in preventing kidney damage from recurrent urinary tract infections (UTIs).

Area of Science:

  • Genetics
  • Pediatric Nephrology
  • Immunology

Background:

  • Recurrent urinary tract infections (UTIs) in children can lead to permanent kidney damage, particularly in those with high-grade vesicoureteral reflux (VUR).
  • Scar tissue formation is a key factor in long-term kidney damage associated with VUR.
  • The Toll-like receptor 4 (TLR4) gene plays a role in the body's resistance to UTIs and its polymorphisms have been linked to recurrent UTIs and kidney scarring.

Purpose of the Study:

  • To investigate the association between Toll-like receptor 4 (TLR4) gene polymorphism and the development of kidney scarring in children diagnosed with VUR.

Main Methods:

  • A cross-sectional study involving 49 pediatric patients with recurrent UTIs and primary VUR.
  • Patients were categorized into two groups: those with kidney scarring (26 patients) and those without (23 patients).
  • Toll-like receptor 4 (TLR4) gene polymorphisms were analyzed using Next Generation Sequencing.

Main Results:

  • A significantly higher prevalence of TLR4 gene polymorphism was observed in the compound heterozygous group with kidney scarring compared to the scar-free group (p=0.03).
  • Specific TLR4 gene polymorphisms (c.958T>C, c.942A>G, c.776A>G, c.1076C>T, c.896AT, c.1078C>T) were more frequently found in the scarring group.
  • The gene polymorphisms c.942A>G and c.776A>G were identified for the first time in patients with scar tissue within this study cohort.

Conclusions:

  • The increased incidence of certain TLR4 gene polymorphisms in children with kidney scarring suggests a potential genetic predisposition contributing to permanent kidney damage.
  • These genetic variations may impact the effectiveness of the immune response against UTIs, leading to scar formation.
  • Environmental factors, such as untreated UTIs, likely interact with genetic predisposition in the development of kidney scarring.

Keywords:
Next Generation SequencingToll-Like Receptor 4Urinary tract infectionVesico-ureteral reflux

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