Platelet-activating factor acetylhydrolase gene mutation in Japanese children with Escherichia coli O157-associated hemolytic uremic syndrome

血小板活化因子(PAF)可能参与了大肠杆菌0157相关性溶血性尿毒症综合征(HUS)的发病过程。PAF乙酰水解酶将PAF降解为非活性产物。在这项研究中，我们调查了PAF乙酰水解酶基因突变(994位G到T颠换)是否与日本儿童的HUS有关。应用聚合酶链式反应技术对50例日本儿童和100例健康日本儿童进行了PAF乙酰水解酶基因(G994T)点突变的检测。确定PAF乙酰水解酶G994T基因突变与HUS临床特征的关系。HUS患者的基因频率和等位基因频率与正常对照组无明显差异。GT基因携带者的平均少尿持续时间明显长于GG基因携带者(p=0.012)。突变等位基因(GT)杂合子(GT)的15名患者中有11名(73%)需要透析，而35名野生型纯合子(GG)中只有13名(37%)需要透析(p=0.030)。GT基因携带者血浆PAF乙酰水解酶活性显著低于GG基因携带者(p&lt；0.0001)。总之，我们已经证明了G994T PAF乙酰水解酶基因突变与肾损害的严重程度有关。我们的研究表明，对患有O157相关HUS的日本儿童的PAF乙酰水解酶基因突变的分析可能有助于预测HUS的严重程度。

Platelet-activating factor (PAF) may be involved in the pathogenesis of Escherichia coli 0157-associated hemolytic uremic syndrome (HUS). PAF is degraded to inactive products by PAF acetylhydrolase. In this study we investigated whether or not a PAF acetylhydrolase gene mutation (G to T transversion at position 994) is involved in HUS in Japanese children. A point mutation in the PAF acetylhydrolase gene (G994T) was identified using the polymerase chain reaction in 50 Japanese children with E. coli 0157-associated HUS and 100 healthy Japanese. We then determined the relationship between the PAF acetylhydrolase G994T gene mutation and clinical features of HUS. There was no difference in the genotype and allele frequencies between patients with HUS and normal controls. The mean duration of oligoanuria was significantly longer in patients with the GT genotype than in those with the GG genotype (p = 0.012). While eleven of the 15 patients (73 %) who were heterozygous for the mutant allele (GT) required dialysis, only 13 of the 35 wild-type homozygotes (GG) (37 %) required dialysis (p = 0.030). The mean plasma PAF acetylhydrolase activity was significantly lower in patients with the GT genotype than in those with the GG genotype (p<0.0001). In conclusion, we have demonstrated an association between the G994T PAF acetylhydrolase gene mutation and the severity of renal damage m E. coli 0157-associated HUS. Our study suggests that analysis of the PAF acetylhydrolase gene mutation in Japanese children with E coli O157- associated HUS may allow the prediction of the severity of HUS.