Deficiency of platelet-activating factor acetylhydrolase is a severity factor for asthma

Asthma, a family of airway disorders characterized by airway inflammation, has an increasing incidence worldwide. Platelet-activating factor (PAF) may play a role in the pathophysiology of asthma. Its proinflammatory actions are antagonized by PAF acetylhydrolase. A missense mutation (V279F) in the...

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Bibliographic Details
Published in:The Journal of clinical investigation 1999-04, Vol.103 (7), p.989-997
Main Authors: Stafforini, D M, Numao, T, Tsodikov, A, Vaitkus, D, Fukuda, T, Watanabe, N, Fueki, N, McIntyre, T M, Zimmerman, G A, Makino, S, Prescott, S M
Format: Article
Language:English
Subjects:
1-Alkyl-2-acetylglycerophosphocholine Esterase
Adolescent
Adult
Aged
Amino Acid Sequence
Asthma - epidemiology
Asthma - genetics
Asthma - physiopathology
Base Sequence
Binding Sites
Child
Female
Genotype
Homozygote
Humans
Japan - epidemiology
Male
Middle Aged
Molecular Sequence Data
Mutation
Phospholipases A - blood
Phospholipases A - deficiency
Polymorphism, Genetic
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Summary:Asthma, a family of airway disorders characterized by airway inflammation, has an increasing incidence worldwide. Platelet-activating factor (PAF) may play a role in the pathophysiology of asthma. Its proinflammatory actions are antagonized by PAF acetylhydrolase. A missense mutation (V279F) in the PAF acetylhydrolase gene results in the complete loss of activity, which occurs in 4% of the Japanese population. We asked if PAF acetylhydrolase deficiency correlates with the incidence and severity of asthma in Japan. We found that the prevalence of PAF acetylhydrolase deficiency is higher in Japanese asthmatics than healthy subjects and that the severity of this syndrome is highest in homozygous-deficient subjects. We conclude that the PAF acetylhydrolase gene is a modulating locus for the severity of asthma.
ISSN:0021-9738
DOI:10.1172/jci5574