Platelet-activating factor acetylhydrolase gene mutation in Japanese nephrotic children.

日本肾病儿童血小板激活因子乙酰水解酶基因突变。

• 批准号: 10670997
• 负责人: YOSHIKAWA Norishige
• 金额: $ 2.37万
• 依托单位: Kobe University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1999
• 资助国家: 日本
• 起止时间: 1999 至 2000
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10670997/
• 关键词: Japanese children; steroid-responsive nephrotic syndrome; relapse; mutations; Platelet-activating factor; Platelet-activating factor acetylhydrolase; gene mutation

Platelet-activating factor (PAF) may be involved in the pathogenesis of steroid-responsive nephrotic syndrome (SRNS). PAF is degraded to inactive products by PAF acetylhydrolase. We have investigated whether PAF acetylhydrolase gene mutation (G994T) is involved in SRNS in Japanese children. We identified a point mutation in the PAF acetylhydrolase gene (G to T transversion at position 994) using the polymerase chain reaction in 101 Japanese children with SRNS and 100 healthy Japanese. We then determined the relationship between the PAF acetylhydrolase G994T gene mutation and relapse of nephrotic syndrome. There was no difference in the genotype and allele frequencies between patients with SRNS and normal controls. The mean number of relapses during the first year after onset was significantly higher in the 26 patients who were heterozygous for the mutant allele (GT) than in 75 wild-type homozygotes (GG) (2.61±1.98 vs. 1.33±1.35 ; p=0.0019). Patients with the mutant (GT) genotype relapsed more often than patients with the wild-type (GG) genotype (xィイD12ィエD1)=15.8, p=0.0033). We conclude that analysis of the PAF acetylhydrolase gene mutation at position 994 in Japanese children with SRNS allows the identification of patients who are more likely to have disease relapse.

血小板活化因子(PAF)可能参与了激素反应性肾病综合征(SRNS)的发病过程。PAF乙酰水解酶将PAF降解为非活性产物。我们调查了PAF乙酰水解酶基因突变(G994T)是否与日本儿童的SRNS有关。我们用聚合酶链式反应在101名患有SRNS的日本儿童和100名健康的日本儿童中发现了PAF乙酰水解酶基因的点突变(994位G到T颠换)。然后，我们确定了PAF乙酰水解酶G994T基因突变与肾病综合征复发的关系。SRNS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。26例突变等位基因(GT)杂合子患者发病后1年内的平均复发次数显著高于75例野生型纯合子患者(2.61±1.98vs.1.33±1.35；P=0.0019)。突变(GT)基因携带者的复发频率高于野生型(GG)基因携带者(xィイD12ィエD1)=15.8，P=0.0033。我们的结论是，对患有SRNS的日本儿童的PAF乙酰水解酶基因994位突变的分析可以识别出更有可能复发的患者。

项目成果

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Yoshikawa N, Iijima K and Ito H: "Cyclosporin treatment in children with steroid-dependent nephrotic syndrome"Clin Exp Nephrol. 10. S27-33 (1999)

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Tanaka R,Yoshikawa N et al.: "Role of platelet-activating factor acetylhudrolase gene mutation in Japanese childhood immunoglobulin A nephropathy"Am J Kidney Dis. 34. 289-295 (1999)

Tanaka R、Yoshikawa N 等人：“血小板活化因子乙酰氢解酶基因突变在日本儿童免疫球蛋白 A 肾病中的作用”Am J Kidney Dis。

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Noguchi K,Yoshikawa N et al.: "Activated mesangial cells produce vascular permeability factor in early-stage mesangial proliferative glomerulonephritis."J Am Soc Nephrol. 9. 1815-1825 (1998)

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