Lack of evidence for associations between plasma platelet-activating factor acetylhydrolase deficiency and...

Platelet-activating factor (PAF) is a potent phospholipid mediator that plays various roles in neuronal function and brain development. It is involved in NMDA receptor function. Release and degradation of PAF is controlled by intracellular and plasma PAF-acetylhydrolase (PAFAH). The plasma PAFAH gene (PLA2G7) is located on chromosome 6p. A previous study showed weak associations of the Ile198Thr and Val379Ala polymorphisms of this gene with schizophrenia that did not reach statistical significance after correction for multiple comparisons. Another study showed that a functional alteration of the enzyme with these two polymorphisms is likely, but the magnitude may be modest. Approximately 4% of the Japanese population lack plasma PAFAH because of a loss-of-function mutation (Val279Phe) in the PAFAH gene. Thus, the Val279Phe mutation is useful for examining whether a causal relation exists between PAFAH function and schizophrenia. We looked for an association between the Val279Phe mutation and schizophrenia in 191 Japanese patients with schizophrenia and in 188 Japanese controls. Similar genotypic and allelic distributions were observed in the two groups. These observations indicate that functional differences in the plasma form of PAFAH do not play a substantial role in the etiology of schizophrenia. However, the present study leaves open the possibility that other isoforms are involved.