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Platelet-activating factor acetylhydrolase gene mutation in Japanese children with Escherichia coli

Platelet-activating factor acetylhydrolase gene mutation in Japanese children with Escherichia coli O157:H7-associated hemolytic uremic syndrome. Xu H, Iijima K, Shirakawa T, Shiozawa S, Miwa M, Yamaoka K, Kawamura N, Nakamura H, Yoshikawa N. American Journal of Kidney Diseases 2000;36(1):42-46.

ABSTRACT:

Platelet-activating factor (PAF) may be involved in the pathogenesis of Escherichia coli O157:H7-associated hemolytic uremic syndrome (HUS). PAF has a multitude of biological effects pertinent to glomerular injury in the kidney, and there is increasing evidence that PAF is involved in the pathogenesis of glomerulonephritis and nephrotic syndrome. PAF is degraded to inactive products by an enzyme called PAF acetylhydrolase. Alterations in the activity of this enzyme have been reported in several disease states and may contribute to the pathogenesis of these conditions. There is an inherited form of PAF acetylhydrolase deficiency and has been observed only in the Japanese population. This deficiency is the result of gene mutations. This study investigated the effects of PAF acetylhydrolase gene mutation on the incidence and severity of HUS among Japanese children. Significant differences were found between the three genotypes studied, with the G994T (GT) genotype more likely to be associated with lower PAF acetylhydrolase activity, longer duration of oligoanuria, and the need for dialysis. At follow-up, 48 of the 50 children with HUS showed normal renal function, and 2 children with the GT genotype showed chronic renal insufficiency. The findings suggest that a reduction in PAF acetylhydrolase activity leads to an accumulation of PAF in patients with the GT genotype. This may then bring about changes characteristic of HUS. An analysis of the gene mutation in Japanese children with E. coli O157-associated HUS may allow the prediction of the severity of HUS. It is possible that therapy with a PAF receptor antagonist may reduce or prevent renal injury in patients with HUS.