Genetic analysis in children with Escherichia coli O157-associated hemolytic uremic syndrome

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Hemolytic uremic syndrome(HUS) is a significant cause of acute renal failure in children. Verotoxin(VT)-producing Escherichia coli(E.coli)(VTEC), particularly those of serogroup O157:H7, are the major cause of hemorrhagic colitis and are responsible for most cases of HUS. E.coli O157 produce large amounts of VT, which traverses polarized gastrointestinal epithelial cells, and gains the systemic circulation. It acts in initiating damage to target organs, such as kidney. Recently, a number of polymorphisms in human immunoregulatory genes have been reported Both the tumor necrosis factor-□(TNF-□) and interleukin-1□(IL-1□) gene loci contain polymorphisms that are associated with the increased secretion of TNF-□ and IL-1□^^〜__・ We therefore postulated that immunoregulatory gene polymorphisms might have an important role in the pathogenesis of HUS. To test this hypothesis, we investigated the effect of (1)TNF-□ promoter, (2)TNF-□, (3)IL-1□, (4)IL-1 receptor antagonist(IL-1RA) and (5)IL-1 typ … More e 1 receptor promoter(IL-1RI) gene polymorphisms on the incidence and the severity of Japanese children with VTEC associated HUS. We studied 48 consecutive Japanese pediatric patients with VTEC-associated HUS from eight hospitals in Japan. A total of 78 unrelated Japanese adult healthy volunteers were also studied as controls. Analysis of the genotype and allele frequencies of the five immunoregulatory genes was performed in the patients with VTEC-associated HUS and the control population. There were no significant differences in genotype and allele between patients with VTEC-associated HUS and healthy controls. There were no significant differences in age at onset, maximum blood urea nitrogen, maximum serum creatinine, duration of oligoanuria, ratio of patients requiring dialysis, minimum hemoglobin, minimum platelet count and ratio of patients with seizure among each genotype. In conclusion, we have demonstrated no efffect of immunoregulatory gene polymorphisms on the incidence and the severity of Japanese children with VTEC associated HUS. Less