A polymorphism in the PDLIM5 gene associated with gene expression and schizophrenia
A polymorphism in the PDLIM5 gene associated with gene expression and schizophrenia
复制标题
DOI：
10.1016/j.biopsych.2005.07.041
复制
发表时间：
2006-03-01
影响因子：
10.6
通讯作者：
Arinami, T
中科院分区：
文献类型：
--
作者：
Horiuchi, Y;Arai, M;Arinami, T
最近对精神分裂症患者死后大脑的DNA微阵列分析结果显示，PDZ和LIM结构域5基因（PDLIM5）的表达增加。在本研究中，我们研究了PDLIM5的多态性是否与精神分裂症有关，我们在24名日本精神分裂症患者中筛选了PDLIM5的突变，并在日本病例对照人群（总样本，278名精神分裂症患者和462名对照受试者）中评估了已鉴定的多态性与精神分裂症的相关性。应用实时定量聚合酶链反应（PCR）技术检测34例精神分裂症患者死后前额叶皮质PDLIM5的表达。电泳迁移率变动分析（EMSA）检测多态性是否影响核蛋白结合。我们在PDLIM5中鉴定了27个多态性，并发现该基因5'区的多态性（rs2433320和rs2433322）与精神分裂症之间存在关联（p = .004）。实时定量PCR显示，这些多态性影响基因表达（p = 0.007）。EMSA结果显示，PDLIM5基因rs2433320多态性位点与核蛋白的结合方式不同，提示PDLIM5基因可能与精神分裂症的遗传易感性有关。
Results of recent DNA microarray analyses of postmortem brains of patients with schizophrenia revealed that expression of the PDZ and LIM domain 5 gene (PDLIM5) is increased. In the present study, we examined whether polymorphisms in PDLIM5 are associated with schizophrenia.We screened for mutations in PDLIM5 in 24 Japanese patients with schizophrenia and evaluated the associations of the identified polymorphisms with schizophrenia in a Japanese case-control population (total samples, 278 schizophrenia patients and 462 control subjects). Expression of PDLIM5 was quantified by real-time quantitative polymerase chain reaction (PCR) in postmortem prefrontal cortex of 34 schizophrenia patients. Electrophoretic mobility shift assay (EMSA) was performed to examine whether a polymorphism influences nuclear protein binding.We identified 27 polymorphisms in PDLIM5 and found associations between polymorphisms (rs2433320 and rs2433322) in the 5' region of the gene and schizophrenia (p = .004). Real-time quantitative PCR revealed that these polymorphisms influenced gene expression (p = .007). An EMSA showed that the different tales of the rs2433320 polymorphism bound differently to nuclear proteins.These results suggest that PDLIM5 might play a role in genetic susceptibility to schizophrenia.