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.