Association between BanI genotype and increased phospholipase A2 activity in schizophrenia
Association between BanI genotype and increased phospholipase A2 activity in schizophrenia
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DOI：
10.1007/s00406-007-0736-0
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发表时间：
2007-09-01
影响因子：
4.7
通讯作者：
Gattaz, Wagner F.
中科院分区：
文献类型：
--
作者：
Barbosa, Nadia R.;Junqueira, Ricardo M.;Gattaz, Wagner F.
磷脂酶A2 （PLA2）是膜磷脂代谢的一个关键酶家族。几项研究报告了精神分裂症患者血液和大脑PLA2活性增加，这表明该疾病中磷脂代谢紊乱。此外，细胞质PLA2基因的遗传变异已被报道与精神分裂症有关。这些数据表明，PLA2编码基因的变异可能是增加精神分裂症易感性的候选者。在这项研究中，我们研究了血小板中PLA2活性与1q25染色体上PLA2 （4A组）基因中BanI多态性位点之间的可能关联。我们招募了75名精神分裂症患者（DSM-IV）和68名健康对照，并进行了PCR检测。用放射酶法测定血小板胞浆内聚乳酸(2)活性。A2等位基因和A2A2基因型在精神分裂症患者中的出现频率高于对照组（p < 0.005和p < 0.05）。当我们根据基因型对受试者进行分类时，我们发现A2A2基因型患者PLA2活性（29.6 +/- 5.1 pMol/mg蛋白/min）显著高于A1A2基因型患者（20.8 +/- 3.6 pMol/mg蛋白/min， p < 0.001）或A1A1基因型患者（15.9 +/- 5.1 pMol/mg蛋白/min， p < 0.001）。同样在对照组中，A2等位基因携带者（A1A2和A2A2）的PLA2活性高于A1A1组（p = 0.004）。我们的数据表明，BanI基因型与血小板中PLA2G4A活性之间存在关联，并且等位基因A2的存在可能通过PLA2活性的增加而增加精神分裂症的风险。
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 PLA(2) 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.