The genetic variation of RELN expression in schizophrenia and bipolar disorder.
The genetic variation of RELN expression in schizophrenia and bipolar disorder.
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DOI：
10.1371/journal.pone.0019955
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Shifman S
中科院分区：
文献类型：
--
作者：
Ovadia G;Shifman S
Reelin在大脑的发育和功能中起着重要作用，并与不同的神经精神疾病有关。为了进一步阐明reelin与精神疾病之间的联系，我们研究了影响reelin基因（reelin gene，RELN）及其不同亚型表达的因素。我们研究了精神分裂症和双相情感障碍患者以及未受影响的对照组的死后脑样本中的总表达、等位基因表达和两种替代性的CINN亚型。我们没有发现在精神分裂症或双相情感障碍患者中，PDRN的总表达量显著降低。然而，我们确实发现了短的cDNAN亚型的比例显着减少，在双相情感障碍中缺失C-末端区域，以及精神分裂症中cDNAN等位基因表达的不平衡。此外，我们还检测了rs7341475基因表达变异与女性精神分裂症相关的内含子SNP之间的关系。我们没有发现rs7341474与女性或整个样本中的cDNAN总表达之间存在关联。然而，我们观察到一个名义上显着的影响，基因型的性别相互作用的变化，微外显子跳跃。具有rs7341475（GG）风险基因型的女性具有更高比例的微外显子跳跃，这是脑外组织中占主导地位的亚型，而男性则具有相反的趋势。最后，我们测试了基因区域中的83个SNP，以确定其与CDPN表达变异的关联性，但均不具有显著性。我们的研究进一步支持了SNPs功能障碍和精神疾病之间的联系，并为精神分裂症相关SNP提供了可能的功能作用。然而，这项研究中观察到的正相关性需要进一步复制，因为它可能对理解精神分裂症和双相情感障碍的生物学原因有影响。
Reelin plays an important role in the development and function of the brain and has been linked to different neuropsychiatric diseases. To further clarify the connection between reelin and psychiatric disorders, we studied the factors that influence the expression of reelin gene (RELN) and its different isoforms. We examined the total expression of RELN, allelic expression, and two alternative RELN isoforms in postmortem brain samples from patients with schizophrenia and bipolar disorder, as well as unaffected controls. We did not find a significant reduction in the total expression of RELN in schizophrenia or bipolar disorder. However, we did find a significant reduction of the proportion of the short RELN isoform, missing the C-terminal region in bipolar disorder, and imbalance in the allelic expression of RELN in schizophrenia. In addition, we tested the association between variation in RELN expression and rs7341475, an intronic SNP that was found to be associated with schizophrenia in women. We did not find an association between rs7341474 and the total expression of RELN either in women or in the entire sample. However, we observed a nominally significant effect of genotype-by-sex interaction on the variation in microexon skipping. Women with the risk genotype of rs7341475 (GG) had a higher proportion of microexon skipping, which is the isoform predominant in tissues outside the brain, while men had the opposite trend. Finally, we tested 83 SNPs in the gene region for association with expression variation of RELN, but none were significant. Our study further supports the connection between RELN dysfunction and psychiatric disorders, and provides a possible functional role for a schizophrenia associated SNP. Nevertheless, the positive associations observed in this study needs further replication as it may have implications for understanding the biological causes of schizophrenia and bipolar disorder.
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影响因子：
5.3
作者：
DArcangelo, G;Nakajima, K;Curran, T
通讯作者：
Curran, T
DOI：
10.1002/ajmg.b.31093
发表时间：
2010-09-01
影响因子：
2.8
作者：
Ben-David, Eyal;Shifman, Sagiv
通讯作者：
Shifman, Sagiv
影响因子：
4.8
作者：
Nakano, Yoshimi;Kohno, Takao;Hattori, Mitsuharu
通讯作者：
Hattori, Mitsuharu
影响因子：
4.2
作者：
Kohno, Takao;Nakano, Yoshimi;Hattori, Mitsuharu
通讯作者：
Hattori, Mitsuharu
影响因子：
--
作者：
Costa, E;Chen, Y;Guidotti, A
通讯作者：
Guidotti, A