Loss of activity of plasma platelet-activating factor acetylhydrolase due to a novel Gln281-->Arg mutation.
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.
Yamada
Y
Y
Department of Geriatric Research, National Institute for Longevity Sciences, Obu, Aichi, Japan.
Yokota
M
M
D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase; D001120:Arginine; D001483:Base Sequence; D002318:Cardiovascular Diseases / Q000201:enzymology* / Q000235:genetics; D004247:DNA / Q000737:chemistry; D005260:Female; D005838:Genotype; D005973:Glutamine / Q000235:genetics*; D006801:Humans; D007564:Japan; D008297:Male; D016297:Mutagenesis, Site-Directed; D009154:Mutation; D010741:Phospholipases A / Q000097:blood / Q000235:genetics*; D011994:Recombinant Proteins / Q000378:metabolism
D011994:Recombinant Proteins; D005973:Glutamine; D004247:DNA; D001120:Arginine; D010741:Phospholipases A; D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase