Polymorphisms of the TNF-α, ACE, PAI-1 and MTHFR Genes, and Renal Scarring in Infants with First Febrile Urinary Tract Infection

Abstract

Background: There is no doubt that genetic predisposition to Febrile Urinary Tract Infection (FUTI), recurrent UTI and Renal Scarring (RS) exists in addition to well-known risk factors. Aims:To determine whether Deoxyribonucleic Acid (DNA) polymorphisms in the Tumor Necrosis Factor alpha (TNF-α), Angiotensin-Converting Enzyme (ACE), Plasminogen Activator Inhibitor -1 (PAI-1), and Methylenetetrahydrofolate Reductase (MTHFR) gene were associated with evolution to renal scars following a first FUTI in infants. Methods:The study included 100 children (84 girls, 16 boys) with first FUTI at age up to 1 year. The study was performed at the Clinical Center University of Sarajevo (CCUS), Pediatric Clinic. The diagnosis was based on the clinical, laboratory findings and imaging procedures: ultrasonography, voiding cystourethrography (VCUG) and, initial and control static renal scintigraphy (DMSA renal scan). The gene polymorphisms of TNF-α, ACE, PAI-1, and MTHFR were determined based on amplification by the Polymerase Chain Reaction (PCR). The distribution of these four genotypes and the allele frequencies were compared between different groups of patients with first FUTI.Results: Results showed that 66 infants had Acute Pyelonephritis (APN), 22 had Vesicoureteral Reflux (VUR) and 18 had RS. We did not find significant difference in the individual representation of specific polymorphism of the examined genes between patients with APN, VUR and RS. But, when we used the regression analysis we were found that all investigated genes together have influence in 67% of cases in the prediction of APN, VUR and RS in children with first FUTI.Conclusions: Although our study supports the belief that genetic variations in TNF-α, ACE, PAI-1 and MTHFR genes together may predispose renal scar, more extensive and comprehensive research and study of the role of polymorphism of different genes in RS after first FUTI is necessary.