The prevalence of plasma platelet-activating factor (PAF) acetylhydrolase deficiency was investigated in 477 healthy Japanese individuals and 985 patients with various cardiovascular diseases. The genotype for this enzyme with regard to a G994-->T mutation (MM, normal; Mm, heterozygote; mm, mutant homozygote) was determined by an allele-specific polymerase chain reaction in 80 subjects shown to have no or low plasma activity (<10 nmol/min/ml). In 72 subjects, the genotype was consistent with plasma enzyme activity; 44 individuals with no activity were mm, and 28 with low activity were Mm. However, eight subjects with the MM genotype showed plasma enzyme activities of <10 nmol/min/ml. Determination of the DNA sequence of exon 9 of the plasma PAF acetylhydrolase gene in these eight subjects revealed a previously unidentified A1001-->G missense mutation, resulting in a Gln281-->Arg substitution, in a 72-year-old woman with coronary artery disease, essential hypertension, and no plasma enzyme activity. Site-directed mutagenesis in vitro showed that the corresponding recombinant mutant protein lacked PAF acetylhydrolase activity. Thus, the Gln281-->Arg substitution appears responsible for the loss of plasma PAF acetylhydrolase activity.

译文

在477名健康的日本人和985名患有各种心血管疾病的患者中,研究了血浆血小板活化因子 (PAF) 乙酰水解酶缺乏症的患病率。关于G994->T突变 (MM,正常; Mm,杂合子; mm,突变纯合子) 的该酶的基因型是通过等位基因特异性聚合酶链反应确定的,在80名受试者中显示无或低血浆活性 (<10 nmol/min/ml)。在72名受试者中,基因型与血浆酶活性一致; 44个无活性的个体为mm,28个低活性的个体为Mm。然而,具有MM基因型的八名受试者的血浆酶活性 <10 nmol/min/ml。在这八名受试者中测定血浆PAF乙酰水解酶基因第9外显子的DNA序列,发现先前未鉴定的A1001->G错义突变,导致Gln281->Arg取代,患有冠状动脉疾病,原发性高血压,没有血浆酶活性。体外定点诱变表明,相应的重组突变蛋白缺乏PAF乙酰水解酶活性。因此,Gln281->Arg取代似乎是造成血浆PAF乙酰水解酶活性丧失的原因。

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