Evidence for an association between plasma platelet-activating factor acetylhydrolase deficiency and increased risk of childhood atopic asthma.
Platelet-activating factor (PAF), which has been implicated in the pathophysiology of inflammation in asthma, is degraded and inactivated by PAF acetylhydrolase (PAFAH). Approximately 4% of the Japanese population lacks plasma PAFAH due to a loss-of-function variant (Val279Phe) in the PAFAH gene. Although lack of PAFAH activity is thought to be a risk factor for asthma, there are conflicting findings concerning association between the Val279Phe variant and asthma. In this study, we conducted transmission disequilibrium tests of 118 Japanese parent-child trios identified through mite-sensitive atopic asthmatic children. A case-control study was also carried out. The Phe279/Phe279 genotype was found more frequently in children with atopic asthma (13%) than in their parents (6%) or in controls (4%). Results of the genotypic transmission test were significant, and the Phe279/Phe279 genotype was transmitted preferentially to asthmatic children. Our data support an association between deficiency in PAFAH activity and atopic asthma.
Ito
Seiko
S
Department of Medical Genetics, Institute of Basic Medical Sciences, Institute of Clinical Medicine, University of Tsukuba, Japan.
Noguchi
Emiko
E
Shibasaki
Masanao
M
Yamakawa-Kobayashi
Kimiko
K
Watanabe
Hideki
H
Arinami
Tadao
T
D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase; D000328:Adult; D000368:Aged; D001249:Asthma / Q000201:enzymology / Q000209:etiology*; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007564:Japan; D008297:Male; D010741:Phospholipases A / Q000172:deficiency* / Q000235:genetics; D011110:Polymorphism, Genetic
D010741:Phospholipases A; D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase