Association study of H2AFZ with schizophrenia in a Japanese case–control sample
Association study of H2AFZ with schizophrenia in a Japanese case–control sample
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日本病例对照样本中 H2AFZ 与精神分裂症的关联研究
DOI：
10.1007/s00702-014-1332-x
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发表时间：
2015
影响因子：
3.3
通讯作者：
T. Nishikawa
中科院分区：
文献类型：
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作者：
Daisuke Jitoku;N. Yamamoto;Y. Iwayama;T. Toyota;Momo Miyagi;T. Enokida;Yuri Tasaka;M. Umino;A. Umino;A. Uezato;Y. Iwata;Katsuaki Suzuki;M. Kikuchi;T. Hashimoto;N. Kanahara;A. Kurumaji;T. Yoshikawa;T. Nishikawa
人们普遍认为N-甲基-d-天冬氨酸(NMDA)型谷氨酸受体功能障碍可能参与了精神分裂症的病理生理过程。最近的一些microRNA(MiRNA)研究表明，精神分裂症患者死后脑内与谷氨酸系统相关的miR-132和miR-212的表达发生了变化。在这里，我们试图进一步了解精神分裂症、NMDA受体、这些miRNAs控制的分子级联以及这两个miRNAs共同预测的靶基因之间的关系。我们重点研究了H_2AFZ(编码H_2A组蛋白家族，成员Z)基因，在我们的筛选研究中，该基因的表达被一种类似精神分裂症的NMDA拮抗剂苯环克利定所修饰。通过使用TaqMan系统进行荧光信号滞留的聚合酶链式反应，我们检测了位于H2 AFZ基因周围和内部的四个标签单核苷酸多态(SNPs；SNP01-04)与精神分裂症的遗传关联。受试者是一个日本队列(2012名精神分裂症患者和2170名对照受试者)。在这个队列中，我们没有发现这些SNP与精神分裂症有任何显著的遗传关联。然而，我们观察到SNP02(Rs2276939)在男性精神分裂症患者中存在显著关联(等位基因P=0.003，基因型P=0.008)。单倍型分析显示，由SNP02-SNP03(Rs10014424)-SNP04(Rs6854536)组成的单倍型也与男性精神分裂症患者显著相关(P<0.018)。即使在对多次测试进行校正后，这些相关性仍然显著。提示H_2AFZ基因可能是男性精神分裂症的易感因素，H_2AFZ信号通路的修饰值得从精神分裂症的病理生理学角度进行进一步研究。
It is widely accepted that malfunction of the N-methyl-d-aspartate (NMDA)-type glutamate receptor may be involved in the pathophysiology of schizophrenia. Several recent microRNA (miRNA) studies have demonstrated that the expression of the glutamate system-related miR-132 and miR-212 is changed in postmortem schizophrenic brains. Here we attempted to obtain further insight into the relationships among schizophrenia, the NMDA receptor, the molecular cascades controlled by these miRNAs and commonly predicted target genes of the two miRNAs. We focused on the H2AFZ (encoding H2A histone family, member Z) gene, whose expression was shown in our screening study to be modified by a schizophrenomimetic NMDA antagonist, phencyclidine. By performing polymerase chain reaction with fluorescent signal detention using the TaqMan system, we examined four tag single nucleotide polymorphisms (SNPs; SNP01–04) located around and within the H2AFZ gene for their genetic association with schizophrenia. The subjects were a Japanese cohort (2,012 patients with schizophrenia and 2,170 control subjects). We did not detect any significant genetic association of these SNPs with schizophrenia in this cohort. However, we observed a significant association of SNP02 (rs2276939) in the male patients with schizophrenia (allelic P = 0.003, genotypic P = 0.008). A haplotype analysis revealed that haplotypes consisting of SNP02–SNP03 (rs10014424)–SNP04 (rs6854536) also showed a significant association in the male patients with schizophrenia (P = 0.018). These associations remained significant even after correction for multiple testing. The present findings suggest that the H2AFZ gene may be a susceptibility factor in male subjects with schizophrenia, and that modification of the H2AFZ signaling pathway warrants further study in terms of the pathophysiology of schizophrenia.
影响因子：
--
作者：
Sullivan, PF;Kendler, KS;Neale, MC
通讯作者：
Neale, MC
影响因子：
5.3
作者：
Bahari-Javan, Sanaz;Maddalena, Andrea;Sananbenesi, Farahnaz
通讯作者：
Sananbenesi, Farahnaz
影响因子：
9.8
作者：
Carlson, CS;Eberle, MA;Nickerson, DA
通讯作者：
Nickerson, DA