Horiuchi Yasue, Arai Makoto, Niizato Kazuhiro, Iritani Shyuji, Noguchi Emiko, Ohtsuki Tsuyuka, Koga Minori, Kato Tadafumi, Itokawa Masanari, Arinami Tadao
Department of Medical Genetics, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Ibaraki, Japan.
Biol Psychiatry. 2006 Mar 1;59(5):434-9. doi: 10.1016/j.biopsych.2005.07.041. Epub 2005 Oct 6.
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 alleles of the rs2433320 polymorphism bound differently to nuclear proteins.
These results suggest that PDLIM5 might play a role in genetic susceptibility to schizophrenia.
近期对精神分裂症患者死后大脑进行的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，我们检测了PDLIM5基因多态性是否与精神分裂症相关。
我们对24例日本精神分裂症患者的PDLIM5基因进行了突变筛查，并在一个日本病例对照人群（共278例精神分裂症患者和462例对照者）中评估了所鉴定的多态性与精神分裂症的相关性。通过实时定量聚合酶链反应（PCR）对34例精神分裂症患者死后前额叶皮质中的PDLIM5表达进行了定量分析。进行电泳迁移率变动分析（EMSA）以检测多态性是否影响核蛋白结合。
我们在PDLIM5基因中鉴定出27个多态性，并发现该基因5'区域的多态性（rs2433320和rs2433322）与精神分裂症之间存在关联（p = 0.004）。实时定量PCR显示这些多态性影响基因表达（p = 0.007）。EMSA表明rs2433320多态性的不同等位基因与核蛋白的结合情况不同。
这些结果表明，PDLIM5可能在精神分裂症的遗传易感性中起作用。
