Polymorphisms of the TNF-α and ACE Genes, and Renal Scarring in Infants With Urinary Tract Infection

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Susceptibility to renal scarring is increasingly investigated through polymorphisms of genes regulating inflammation and fibrosis. TNF-alpha and ACE gene polymorphisms have been studied in chronic renal conditions but their role in urinary tract infection and vesicoureteral reflux associated renal scarring is unclear. We investigated the relationship between TNF-alpha A/G and ACE I/D polymorphisms, and renal scarring after urinary tract infection in infants. ACE I/D and TNF-alpha -308 A/G polymorphisms were investigated with restriction fragment length polymorphism analysis in 39 boys and 25 girls with a first urinary tract infection before age 2 years and in 77 controls. Genotype and allele frequencies were compared among children with urinary tract infection with and without renal scarring, and controls. ACE I/D genotype frequencies were similar among infants with urinary tract infection with and without renal scarring, and controls. However, all 6 children with severe renal scarring and impaired renal function bore a D allele, 5 of which were DD homozygotes. D allele was more common in these severely affected children than in their peers with urinary tract infection and mild or no renal scarring (OR 9.92, 95% CI 1.24-79, p = 0.012), and controls (OR 8.03, 95% CI 1.01-64, p = 0.029). No differences were observed in TNF-alpha A/G genotype frequencies among the 3 groups. Presence of vesicoureteral reflux was not related to phenotypes or allele frequencies. Our findings suggest that D allele polymorphism of the ACE gene is associated with urinary tract infection related severe renal scarring in young children.