Aim: We studied the functional polymorphisms of intercellular adhesion molecule-1
(ICAM-1) and toll-like receptor-4 (TLR-4) genes and risk of acute pyelonephritis (APN) in
children attending Assiut University Children’s Hospitals, Egypt, from 2011 to 2015.
Methods: Urinary tract infections (UTIs) were diagnosed in 380 children: 98 had APN and
282 had lower UTIs. Four single-nucleotide polymorphisms in ICAM-1 and TLR-4 genes
were genotyped in all subjects: ICAM-1 rs1799969 Gly241Arg, ICAM-1 rs5498
Glu469Lys, TLR-4 rs4896791 Thr399Ile and TLR-4 rs4896790 Asp299Gly.
Results: Patients with APN were significantly more likely to have AA genotype of the ICAM-
1 rs5498 (1462 A/G) polymorphism (p = 0.04) than children with lower UTIs and the
TLR-4 Asp299Gly GG genotype (p = 0.002) and G allele (p = 0.006) than healthy
controls. The association with the ICAM-1 Glu469Lys (1462A/G) was less evident. The GG
genotype was associated with a modest relative risk of 1.4 (p = 0.1) of developing APN,
but was not an independent odds ratio, at 1.2 (p = 0.48).
Conclusion: Functional variants in ICAM-1 and TLR-4 genes were increasingly common in
children with febrile UTIs with renal parenchymal involvement, but the ICAM-1 Glu469Lys
(1462A/G) association was less evident. TLR4 Asp299Gly might independently increase
renal parenchymal infection rather than renal scarring.