| Project/Area Number |
12671039
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Kidney internal medicine
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| Research Institution | Wakayama Medical University |
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Principal Investigator |
YOSHIKAWA Norishige Wakayama Medical University, School of Medicine, Professor, 医学部, 教授 (10158412)
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| Co-Investigator(Kenkyū-buntansha) |
SUZUKI Hiroyuki Wakayama Medical University, School of Medicine, Lecturer, 医学部, 講師 (80196865)
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| Project Period (FY) |
2001 – 2002
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| Project Status |
Completed (Fiscal Year 2001)
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| Budget Amount *help |
¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 2001: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2000: ¥2,200,000 (Direct Cost: ¥2,200,000)
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| Keywords | Platelet-activating factor / Platelet-activating factor acetylhydrolase / gene mutation / hemolytic uremic syndrome |
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| Research Abstract |
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.
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