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

Vesicoureteral reflux (VUR) is an important factor in the etiology of recurrent urinary tract infections (UTIs). Permanent kidney damage may develop in children with high-grade VUR in the long term. This damage may progress with the development of scar tissue in some patients. The <i>TLR4</i> gene is an important resistance mechanism, especially against UTIs. <i>TL</i>R4 gene polymorphism is associated with recurrent UTIs and kidney scar development in the long term. This study aimed to examine the relationship between scar development and <i>TLR4</i> gene polymorphism in children with VUR. This cross-sectional study included 49 patients with recurrent UTIs and primary vesicoureteral reflux. Patients were divided into two groups (26 patients with the scar, and 23 patients without scar) according to the presence of scar tissue. <i>TLR4</i> gene polymorphisms of the patients were evaluated by Next Generation Sequencing. The <i>TLR4</i> gene polymorphism was significantly higher in the compound heterozygous group with scarring than in the group without scarring (p=0.03). Gene polymorphisms, c.958T>C, c.942A>G, c.776A>G, c.1076C>T, c.896A<G, c.1196C>T, c.1078C>T were presented more commonly in the group with scarring. Moreover, gene polymorphisms c.942A>G and c.776A>G were defined for the first time in this study among patients with scar tissue. The higher incidence of some <i>TLR4</i> gene polymorphisms in patients with scarring suggested that these variations might cause permanent kidney damage. In addition to genetic predisposition, environmental factors such as untreated UTIs might also contribute to scar formation.