PAF分解酶基因突变与大肠杆菌O-157所致儿童HUS

Platelet-Activating Factor Acetylhydrolase Gene Mutation in Hemolytic Uremic Syndrome

目的：PAF参与HUS的发病机理。PAF在PAF分解酶的作用不失活。本研究观察PAF分解酶基因突变（第994位点G到T的置换）是否参与了儿童HUS的发生、发展。方法：在50例产毒性大肠杆菌所致HUS患儿和100例健康人中，用PCR方法检测PAF分解酶基因的点突变（G999T）。分析PAF分解酶基因的点突变与HUS临床特点的关系。结果：HUS患儿和健康人均存在PAF分解酶基因的点突变，两者之间在基因型和位点频率分布上无显著差异。但在15例来合型突变（GT）患儿中11例（7％）实施了透析，而35例野生型（GG）中仅13例（37％）需要透析（P＝0．030）。GT基因型患儿的血浆PAF分解酶的活性显著低于GG基因型患儿（P＜0．0001）。结论：PAF分解酶基因突变G994T与产螺旋毒素致病性大肠杆菌O－157关联的HUS肾脏损害的严重程度有关。

objective: Platelet - activating factor (PAF) may be invoved in the pathogenesis of Escherichia coli O157 - associated hernolytic uremic syndrome (HUS). PAF is degraded to inactive preducts by PAF acetylhydrolase. In this study we in vestigated weather or not a PAF acetylhydrolase gene mutation (G to T transversion at POSition 994) is involved in children with HUS. Methords: A point mutation in the PAF acetylhydroase gene was identified using the poymerase chain reaction in 50 Japanese children with E. Coli O157 - associated HUS and 100 healthy Japanese. We then determined the relationship between the PAF acetylhydrolase G944T gene mutation and clinical features of HUS. Results: There was no difference in the genotype and allele frequencies between patients with HUS and normal controls. While of the l5 patients (73 % ) who were heterozyhous 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). Conclusions: We have demonstrated an association between the G994T PAF acetylhydrolase gene mutation and the severity of renal damage in E. Coli o 157 - associated HUS.