Functional variants in intercellular adhesion molecule‐1 and toll‐like receptor‐4 genes are more frequent in children with febrile urinary tract infection with renal parenchymal involvement

• Published in: Acta Paediatrica Vol. 107; no. 2; pp. 339 - 346
• Main Authors: Hussein, Almontaser, Saad, Khaled, Askar, Eman, Zahran, Asmaa M., Farghaly, Hekma, Metwalley, Kotb, Elderwy, Ahmad A.
• Format: Journal Article
• Language: English
• Published: Norway Wiley Subscription Services, Inc 01.02.2018
• Subjects: Adolescent; Case-Control Studies; Cell adhesion; Cell adhesion & migration; Child; Child, Preschool; Children; Escherichia coli - isolation & purification; Female; Fever - etiology; Genotype; Genotypes; Humans; Intercellular adhesion molecule 1; Intercellular Adhesion Molecule-1 - genetics; Kidney - pathology; Kidneys; Male; Parenchymal Tissue - pathology; Polymorphism; Polymorphism, Genetic; Pyelonephritis; Pyelonephritis - etiology; Pyelonephritis - genetics; Renal parenchymal infection; Single-nucleotide polymorphism; TLR4 protein; Toll-Like Receptor 4 - genetics; Toll-like receptors; Urinary tract; Urinary tract infection; Urinary tract infections; Urinary Tract Infections - complications; Urinary Tract Infections - genetics; Urine - microbiology; Urogenital system; Renal parenchymal infection; Urinary tract infection; Pyelonephritis; Intercellular adhesion molecule-1; Polymorphism
• ISSN: 0803-5253; 1651-2227; 1651-2227
• DOI: 10.1111/apa.14118

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.