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

在2003年至2004年的科学研究（C）（2）项目中，我们研究了精神分裂症患者死后大脑扣带皮层和前额叶皮层的基因表达，以确定新的精神分裂症候选基因。1）使用cDNA阵列筛选来自精神分裂症患者扣带皮层或前额叶皮层的样本池。在检测的基因中，33个mRNA增加，22个mRNA减少。进行定量逆转录酶（RT）-PCR、Western印迹或原位杂交分析以确认结果。我们筛选了可能的候选基因中的遗传变异，并研究了精神分裂症与遗传多态性的关联。2）利用差异显示技术，我们在大鼠延髓核（NAcs）中鉴定了一个受PCP延迟作用调控的基因。获得的cDNA克隆与大鼠突触相关蛋白90/突触后密度-95相关蛋白1（SAPAP 1）相同。使用抗SAPAP 1抗体的免疫定量表明，SAPAP 1的免疫反应性增加，从未经药物治疗的精神分裂症患者死后的大脑NAcs。我们在SAPAP 1/DAP-1基因上发现了一个单核苷酸多态性（1618 A/G）。3）在G蛋白信号调节子10（Regulator of G protein signaling 10，RGS 10）基因中发现了一个新的错义多态性（Val 38 Met）。一项病例对照研究未显示该多态性与精神分裂症之间存在显著关联。

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.