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

Abstract

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 TLR4 gene is an important resistance mechanism, especially against UTIs. TLR4 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 TLR4 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. TLR4 gene polymorphisms of the patients were evaluated by Next Generation Sequencing. The TLR4 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.896AT, 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 TLR4 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.