Association between BanI genotype and increased phospholipase A2 activity in schizophrenia

摘要

Phospholipases A2 (PLA2) are a family of key enzymes in the metabolism of membrane phospholipids. Several studies reported on increased blood and brain PLA2 activity in schizophrenia, which suggest a disordered phospholipid metabolism in the disease. In addition, a genetic variant of a cytosolic PLA2 gene has been reported to be associated with schizophrenia. These data indicate that variants of PLA2 encoding genes are plausible candidates for increasing the susceptibility for schizophrenia. In this study, we investigated a possible association between PLA2 activity in platelets and a polymorphic site for BanI in the PLA2 (group 4A) gene on chromosome 1q25. Seventy-five schizophrenic patients (DSM-IV) and 68 healthy controls were recruited and the PCR assays were performed. A radioenzymatic assay for the cytosolic PLA2 activity in platelets was used. The allele A2 and the genotype A2A2 were more frequent in schizophrenic patients than in controls (p < 0.005 and p < 0.05 respectively). When we assorted the subjects according to their genotypes, we found that PLA2 activity was significantly higher in patients with the A2A2 genotype (29.6 ± 5.1 pMol/mg protein/min) than in those with the A1A2 (20.8 ± 3.6 pMol/mg protein/min, p < 0.001) or A1A1 genotype (15.9 ± 5.1 pMol/mg protein/min, p < 0.001). Also in controls, carriers of the A2 allele (A1A2 and A2A2) had higher PLA2 activity than the A1A1 group (p = 0.004 for both). Our data suggest an association between BanI genotype and PLA2G4A activity in platelets and that the presence of the allele A2 may increase risk for schizophrenia through an increment of PLA2 activity.