Glutamate AMPA receptor subunit 1 gene (GRIA1) and DSM-IV-TR schizophrenia:: A pilot case-control association study in an Italian sample
Glutamate AMPA receptor subunit 1 gene (GRIA1) and DSM-IV-TR schizophrenia:: A pilot case-control association study in an Italian sample
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DOI：
10.1002/ajmg.b.30294
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发表时间：
2006-04-05
影响因子：
2.8
通讯作者：
Barlati, S
中科院分区：
文献类型：
--
作者：
Magri, C;Gardella, R;Barlati, S
谷氨酸能功能障碍是精神分裂症发病机制的主要假说之一。GRLA1基因编码四个（GluR1-4）嗜离子性AMPA受体亚基中的一个（GluR1）。GRLA1是一个很好的精神分裂症易感性候选基因，因为它定位于5q33，这是一个易感性位点存在的区域，独立的全基因组扫描表明，因为它的表达在一些精神分裂症患者的大脑中被发现减少。我们介绍了一项意大利人群的病例对照关联研究数据，该研究涉及整个GRIA1基因的8个多态性。单位点分析显示，两个snp （rs707176, 0.41 vs. 0.31， P= 0.009; rs2963944, 0.41 vs. 0.30， P= 0.007）和一个微卫星（rs10631988，等位基因9:0.40 vs. 0.29， P=0.004）的等位基因分布在病例和对照组中存在显著差异。单倍型分析显示，这些标记的特定单倍型频率增加（C09CC, 0.39 vs. 0.28， P=0.009）。因此，我们的数据表明，GRIA1可能与DSM-IV-TR精神分裂症的易感性有关。(c) 2006 Wiley-Liss, Inc。
Glutamatergic dysfunction is one of the major hypotheses for the pathogenesis of schizophrenia. The GRLA1 gene encodes for one (GluR1) of the four (GluR1-4) ionotropic AMPA receptor subunits. GRLA1 is a good candidate gene for susceptibility to schizophrenia since it maps in 5q33, a region where the presence of susceptibility loci has been suggested by independent genome-wide scans and because its expression has been found to be decreased in the brain of some schizophrenia patients. We present data from a case-control association study on the Italian population with eight polymorphisms spanning the whole GRIA1 gene. Single-locus analysis revealed a significantly different allele distribution in cases and in controls of two SNPs (rs707176, 0.41 vs. 0.31, P = 0.009; rs2963944, 0.41 vs. 0.30, P = 0.007), and one microsatellite (rs10631988, allele 9: 0.40 vs. 0.29, P=0.004). Haplotype analysis showed an increased frequency of a specific haplotype for these markers (C09CC, 0.39 vs. 0.28, P=0.009). Therefore our data indicate that GRIA1 may be involved in susceptibility to DSM-IV-TR schizophrenia. (c) 2006 Wiley-Liss, Inc.