Expression of candidate susceptibility gene in the cingulated cortex of brains from patients with schizophrenia : a postmortem study

在我们2003-2004年的科学研究(C)(2)项目中，我们研究了精神分裂症死后大脑扣带回和前额叶皮质的基因表达，以寻找新的精神分裂症候选基因。1)使用基因芯片从精神分裂症患者的扣带回或前额叶皮质中筛选样本库。在检测的基因中，33个基因表达上调，22个基因表达下调。定量逆转录酶(RT)-聚合酶链式反应、Western印迹或原位杂交分析以证实结果。我们筛选了可能的候选基因的遗传变异，并研究了精神分裂症与遗传多态的关系。2)利用差异显示技术，我们在大鼠伏隔核(NAC)中发现了一个受PCP延迟作用调控的基因。获得的克隆与大鼠突触相关蛋白90/突触后密度相关蛋白1(SAPAP1)完全一致。使用抗SAPAP1抗体的免疫定量表明，未用药的精神分裂症患者死后脑的NAC中SAPAP1的免疫反应性增加。我们发现SAPAP1/DAP-1基因存在单核苷酸多态性(1618A/G)。3)我们在G蛋白信号转导10(RGS10)基因的调节基因中发现了一个新的错义多态(Val38Met)。一项病例对照研究没有显示这种基因多态与精神分裂症之间的显著关联。

In our Scientific Research (C)(2) project from 2003 to 2004, we investigated gene expression in the cingulate and prefrontal cortices of postmortem brains of schizophrenia, in order to identify novel candidate genes for schizophrenia.1)A cDNA array was used to screen pools of samples from the cingulate or prefrontal cortex of patients with schizophrenia. Of the examined genes, 33 mRNA were increased and 22 were decreased. Quantitative reverse transcriptase (RT)-PCR, Western blot, or in situ hybridization analyses were done to confirm the results. We screened for genetic variations in the possible candidate genes and studied the association between schizophrenia and genetic polymorphisms.2)Using differential display, we identified a gene regulated by the delayed action of PCP in rat nucleus accumbens (NAcs). The cDNA clone obtained was identical to rat synapse-associated protein 90/postsynaptic density-95-associated protein 1 (SAPAP1). Immunoquantification using an anti-SAPAP1 antibody indicated that immunoreactivity for SAPAP1 increased in the NAcs of postmorten brains from unmedicated patients with schizophrenia. We identified a single nucleotide polymorphism in the SAPAP1/DAP-1 gene (1618A/G). However, a case-control study did not reveal a significant association between this polymorphism and schizophrenia.3)We found a novel missense polymorphism (Val38Met) in the Regulator of G-protein signaling 10 (RGS10) gene. A case-control study did not show a significant association between this polymorphism and schizophrenia.