TLR-4 polymorphisms and leukocyte TLR-4 expression in febrile UTI and renal scarring

Pediatr Nephrol. 2013 Sep;28(9):1827-35. doi: 10.1007/s00467-013-2478-8. Epub 2013 Apr 24.


Background: In this study, we aimed to determine the relation of TLR-4 Asp299Gly and Thr399Ile polymorphisms and monocyte/neutrophil TLR-4 expression to febrile urinary tract infection (UTI) and renal scar development in children.

Methods: The study was performed in children with a history of febrile UTI. Patients with and without renal scarring were classified as group 1 and group 2, respectively, while the control cases in our previous study were used as the control group (group 3). All three groups were compared for the rate of TLR-4 Asp299Gly and Thr399Ile polymorphisms, and for basal and lipopolysaccharide-stimulated monocyte/neutrophil TLR-4 expression levels.

Results: There were 168 patients (86 in group 1, 82 in group 2) and 120 control cases. Monocyte/neutrophil TLR-4 expression levels were similar in groups 1 and 2. However, both groups had lower TLR-4 expression than group 3. The rate of TLR-4 Asp299Gly polymorphism was not different in all groups. TLR-4 Thr399Ile polymorphism was higher in groups 1 and 2 than in group 3 (14.0, 12.2, and 2.0 %, respectively), while group 1 and group 2 were not different. Furthermore, monocyte TLR-4 expression level was lower in those having TLR-4 Thr399Ile polymorphism than in those without this polymorphism.

Conclusions: Patients with febrile UTI had more frequent TLR-4 Thr399Ile polymorphism and lower monocyte/neutrophil TLR-4 expression. These findings indicate that children carrying TLR-4 Thr399Ile polymorphism and/or having low level of monocyte/neutrophil TLR-4 expression have a tendency to develop febrile UTI. However, we could not show the association of TLR-4 polymorphisms and of TLR-4 expression level to renal scarring.

MeSH terms

  • Child
  • DNA / genetics
  • Female
  • Fever / complications
  • Fever / metabolism
  • Flow Cytometry
  • Humans
  • Kidney / pathology*
  • Leukocytes / metabolism*
  • Lipopolysaccharides / pharmacology
  • Male
  • Monocytes / metabolism
  • Polymerase Chain Reaction
  • Polymorphism, Genetic
  • Polymorphism, Restriction Fragment Length / genetics
  • Pyelonephritis / genetics
  • Pyelonephritis / metabolism
  • Toll-Like Receptor 4 / biosynthesis*
  • Toll-Like Receptor 4 / genetics*
  • Urinary Tract Infections / genetics*
  • Urinary Tract Infections / metabolism*
  • Urinary Tract Infections / pathology


  • Lipopolysaccharides
  • Toll-Like Receptor 4
  • DNA