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

日本大肠杆菌O157相关溶血性尿毒症综合征患儿血小板激活因子乙酰水解酶基因突变

• 批准号: 12671039
• 负责人: YOSHIKAWA Norishige
• 金额: $ 2.05万
• 依托单位: Wakayama Medical University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12671039/
• 关键词: Platelet-activating factor; Platelet-activating factor acetylhydrolase; gene mutation; hemolytic uremic syndrome

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.

血小板活化因子（PAF）可能参与大肠杆菌0157相关性溶血性尿毒综合征（HUS）的发病机制。PAF被PAF乙酰水解酶降解为无活性的产物。在这项研究中，我们调查是否PAF乙酰水解酶基因突变（G到T颠换在位置994）是在日本儿童HUS参与。采用聚合酶链反应技术，在50例日本儿童大肠杆菌中鉴定出PAF乙酰水解酶基因（G994T）的点突变。coli 0157相关HUS和100名健康日本人。然后我们确定PAF乙酰水解酶G994T基因突变与HUS临床特征之间的关系。HUS组与正常对照组基因型和等位基因频率无差异。GT基因型患者少尿的平均持续时间显著长于GG基因型患者（p = 0.012）。15例突变等位基因（GT）杂合子患者中有11例（73%）需要透析，而35例野生型纯合子（GG）中只有13例（37%）需要透析（p = 0.030）。GT基因型患者的平均血浆PAF乙酰水解酶活性显著低于GG基因型患者（p<0.0001）。总之，我们已经证实了G994T PAF乙酰水解酶基因突变与肾损害严重程度之间的关联。coli0157相关HUS。我们的研究表明，在日本儿童与大肠杆菌O157相关的溶血尿毒综合征的PAF乙酰水解酶基因突变的分析可能允许的严重程度的预测溶血尿毒综合征。

项目成果

Xu H, Yoshikawa N et al.: "Platelet-activating factor acetyihydrolase mutation in Japanese children with HUS"Am J Kidney Dis. 32. 42-46 (2000)

Xu H、Yoshikawa N 等：“日本 HUS 儿童中的血小板激活因子乙酰水解酶突变”Am J Kidney Dis。

Xu H, Yashikawa N et al.: "Platelet-activating factor acetylhydrolase mutation in Japanese children with HUS"Am J Kidney Dis. 32. 42-46 (2000)

Xu H、Yashikawa N 等：“日本 HUS 儿童中的血小板激活因子乙酰水解酶突变”Am J Kidney Dis。

Nishimoto K, Yoshikawa N et al.: "PAX2 gene mutation in a family with isolated renal hypoplasia"J Am Soc Nephrol. 12. 1769-1772 (2001)

Nishimoto K、Yoshikawa N 等人：“孤立性肾发育不全家族中的 PAX2 基因突变”J Am Soc Nephrol。

Xu H., Iijima K., Shiozawa S., Shirakawa T., Nakamura H., Yosjizawa N.: "Platelet-activating factor acetylhydrolase mutaion in Japanesechildren with HUS"Am J Kidney Dis. 32. 42-46 (2000)

Xu H.、Iijima K.、Shiozawa S.、Shirakawa T.、Nakamura H.、Yosjizawa N.：“日本 HUS 儿童中的血小板激活因子乙酰水解酶突变”Am J Kidney Dis。

Iijima K, Yoshikawa N et al.: "Immunohistochemical Analysis of Renin Activity in Chronic Cyclosporine Nephropathy in Childhood Nephrotic Syndrome"J Am Soc Nephrol. 11. 2265-2271 (2000)

Iijima K、Yoshikawa N 等人：“儿童肾病综合征慢性环孢素肾病肾素活性的免疫组织化学分析”J Am Soc Nephrol。