Genetic analysis of a functional GRIN2A promoter (GT)n repeat in bipolar disorder pedigrees in humans
Genetic analysis of a functional GRIN2A promoter (GT)n repeat in bipolar disorder pedigrees in humans
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DOI：
10.1016/s0304-3940(03)00501-9
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发表时间：
2003-07-10
影响因子：
2.5
通讯作者：
Yoshikawa, T
中科院分区：
文献类型：
--
作者：
Itokawa, M;Yamada, K;Yoshikawa, T
据推测，谷氨酸能神经传递功能减退是双相情感障碍以及精神分裂症病理生理学的基础。我们检查了 N-甲基-D-天冬氨酸受体 2A 亚基 (GRIN2A) 基因在 16p13.3 上的作用，该区域被认为与双相情感障碍有关，(1) 因为在之前的研究中，我们在该基因的 5' 调控区域中发现了一个功能性和多态性 (GT)n 重复，较长的等位基因显示出较低的转录活性和精神分裂症中的过度代表性，(2) 因为这表明两者之间存在遗传重叠。情感障碍和精神分裂症。基于家族的关联测试发现，在 96 个多重双相谱系中，较长等位基因存在名义上显着的优先传递。这些结果支持低谷氨酸能状态参与双相情感障碍的发病机制的假设。 (C) 2003 Elsevier Science Ireland Ltd. 保留所有权利。
Hypofunction of glutamatergic neurotransmission has been hypothesized to underlie the pathophysiology of bipolar affective disorder, as well as schizophrenia. We examined the role of the N-methyl-D-aspartate receptor 2A subunit (GRIN2A) gene on 16p13.3, a region thought to be linked to bipolar disorder, (1) because in a prior study we identified a functional and polymorphic (GT)n repeat in the 5' regulatory region of the gene, with longer alleles showing lower transcriptional activity and an over representation in schizophrenia, and (2) because of the suggestion of a genetic overlap between affective disorder and schizophrenia. Family-based association tests detected a nominally significant preferential transmission of longer alleles in a panel of 96 multiplex bipolar pedigrees. These results support the hypothesis that a hypoglutamatergic state is involved in the pathogenesis of bipolar affective disorder. (C) 2003 Elsevier Science Ireland Ltd. All rights reserved.