PLA2G4A 的拷贝数缺失会影响精神分裂症的易感性和临床表型。

IF 3 Q2 PSYCHIATRY
Zibo Gao, Xinru Guo, Zhouyang Sun, Songyu Wu, Qianyi Wang, Qianlong Huang, Wei Bai, Changgui Kou
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引用次数: 0

摘要

磷脂酶 A2(PLA2)超家族被认为通过影响细胞膜的脂质平衡参与了精神分裂症的发病机制。我们假设 PLA2 基因拷贝数变异(CNV)可能会影响 PLA2 酶的表达,并与精神分裂症风险相关。这项研究表明,在发现阶段,PLA2G6拷贝数的增加以及PLA2G3、PLA2G4A、PLA2G4F和PLA2G12F的缺失与精神分裂症风险的增加有关。在公开数据集中检测到了涉及六个 PLA2 基因的 CNV 片段,其中包括两个 PLA2G4A 基因特有的缺失片段。随后,在由 806 人组成的验证组中再次证实了 PLA2G4A 基因缺失与精神分裂症易感性之间的关系。PLA2G4A 基因缺失与男性患者的思维贫乏症状和女性患者的色情妄想症状之间存在明显的相关性。此外,酶联免疫吸附试验结果表明,与正常基因型和拷贝数重复基因型的患者相比,PLA2G4A缺失基因型患者的外周血细胞膜PLA2(cPLA2)水平明显下降。这些数据表明,PLA2G4A 基因功能拷贝数缺失通过降低 cPLA2 的表达与精神分裂症的患病风险和临床表型有关,而 cPLA2 的表达可能是精神分裂症易感性的一个指标。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Copy number deletion of PLA2G4A affects the susceptibility and clinical phenotypes of schizophrenia.

Copy number deletion of PLA2G4A affects the susceptibility and clinical phenotypes of schizophrenia.

Phospholipase A2(PLA2) superfamily is recognized as being involved in the pathogenesis of schizophrenia by affecting lipid homeostasis in cell membranes. We hypothesized that PLA2 gene copy number variation (CNV) may affect PLA2 enzyme expression and be associated with schizophrenia risk. This study indicated that in the discovery stage, an increased copy number of PLA2G6 and the deletion of PLA2G3, PLA2G4A, PLA2G4F and PLA2G12F was associated with increased risk of schizophrenia. CNV segments involving six PLA2 genes were detected in publicly available datasets, including two deletion segments specific to the PLA2G4A gene. The relationship between the deletion of PLA2G4A and susceptibility to schizophrenia was then reaffirmed in the validation group of 806 individuals. There was a significant correlation between PLA2G4A deletion and the symptoms of poverty of thought in male patients and erotomanic delusion in females. Furthermore, ELISA results demonstrate a significant decrease in peripheral blood cytosolic PLA2(cPLA2) levels in patients with the PLA2G4A deletion genotype compared to those with normal and copy number duplicate genotypes. These data suggest that the functional copy number deletion in the PLA2G4A gene is associated with the risk of schizophrenia and clinical phenotypes by reducing the expression of cPLA2, which may be an indicator of susceptibility to schizophrenia.

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