Evidence for association of schizophrenia with genetic variation in the 8p21.3 gene, PPP3CC, encoding the calcineurin gamma subunit
Evidence for association of schizophrenia with genetic variation in the 8p21.3 gene, PPP3CC, encoding the calcineurin gamma subunit
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DOI：
10.1073/pnas.1432927100
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发表时间：
2003-07-22
影响因子：
11.1
通讯作者：
Tonegawa, S
中科院分区：
文献类型：
--
作者：
Gerber, DJ;Hall, D;Tonegawa, S
精神分裂症是一种严重的精神疾病，其特征是复杂的遗传模式。前脑特异性CNB基因敲除小鼠表现出一系列与精神分裂症患者行为改变相关的行为异常。为了研究钙调神经磷酸酶功能障碍是否与精神分裂症的病因有关，我们对钙调神经磷酸酶相关基因的初始子集进行了研究，优先考虑那些通过连锁研究映射到先前与精神分裂症有关的位点的基因。在一个大样本的受影响的家庭中的传播不平衡研究检测到PPP3CC基因，它编码的钙调神经磷酸酶γ催化亚基，与疾病的关联。我们的研究结果确定PPP3CC，位于8p21.3，作为一个潜在的精神分裂症易感基因，并支持钙调神经磷酸酶信号的改变有助于精神分裂症的发病机制的建议。
Schizophrenia is a severe psychiatric disorder characterized by a complex mode of inheritance. Forebrain-specific CNB knockout mice display a spectrum of behavioral abnormalities related to altered behaviors observed in schizophrenia patients. To examine whether calcineurin dysfunction is involved in schizophrenia etiology, we undertook studies of an initial subset of calcineurin-related genes, prioritizing ones that map to loci previously implicated in schizophrenia by linkage studies. Transmission disequilibrium studies in a large sample of affected families detected association of the PPP3CC gene, which encodes the calcineurin gamma catalytic subunit, with disease. Our results identify PPP3CC, located at 8p21.3, as a potential schizophrenia susceptibility gene and support the proposal that alterations in calcineurin signaling contribute to schizophrenia pathogenesis.