Analysis of correlation between serum D-serine levels and functional promoter polymorphisms of GRIN2A and GRIN2B genes
Analysis of correlation between serum D-serine levels and functional promoter polymorphisms of GRIN2A and GRIN2B genes
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DOI：
10.1016/j.neulet.2005.10.025
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发表时间：
2006-02-13
影响因子：
2.5
通讯作者：
Yoshikawa, T
中科院分区：
文献类型：
--
作者：
Iwayama, Y;Hashimoto, K;Yoshikawa, T
D-丝氨酸是一种内源性共激动剂，可增加 N-甲基-D-天冬氨酸 (NMDA) 型谷氨酸受体通道的开放。我们之前报道过精神分裂症患者 D-丝氨酸血清水平降低，支持 NMDA 受体介导的神经传递不足的疾病假说。 D-丝氨酸的血清水平被认为反映了大脑中D-丝氨酸的含量。重要的是要了解 D-丝氨酸水平的改变与体内 NMDA 受体表达之间是否存在直接联系，或者这些是否是独立的过程。已知有两种多态性调节 NMDA 受体亚基基因的表达：NR2A 亚基基因 (GRIN2A) 启动子区的 (GT)(n) (rs3219790) 和 NR2B 基因 (GRIN2B) 的 -200T > G (rs1019385)。据报道，这些多态性也与精神分裂症有关。因此，我们检查了精神健康对照、精神分裂症患者和联合组中这两种多态性与 D-丝氨酸血清水平之间的相关性。我们在任何样本组中都没有观察到显着的基因型-表型相关性。然而，在我们得出结论之前，需要对较大样本数量进行分析并检测影响基因表达的额外多态性，如果涉及精神分裂症病理生理学，则NMDA受体表达和D-丝氨酸的血清水平是独立且相加的事件。 (c) 2005 Elsevier Ireland Ltd. 保留所有权利。
D-Serine is an endogenous coagonist that increases the opening of N-methyl-D-aspartate (NMDA)-type glutamate receptor channels. We previously reported a reduction Of D-serine serum levels in schizophrenia, supporting the disease hypothesis of NMDA receptor-mediated hyponeurotransmission. The serum levels Of D-serine are thought to reflect brain D-serine content. It is important to understand whether there is a direct link between the altered D-serine levels and NMDA receptor expression in vivo or whether these are independent processes. Two polymorphisms are known to regulate the expression of NMDA receptor subunit genes: (GT)(n) (rs3219790) in the promoter region of the NR2A subunit gene (GRIN2A) and -200T > G (rs1019385) in the NR2B gene (GRIN2B). These polymorphisms are also reported to be associated with schizophrenia. Therefore, we examined the correlation between these two polymorphisms and D-serine serum levels in mentally healthy controls, schizophrenics and the combined group. We observed no significant genotype-phenotype correlations in any of the sample groups. However, analyses of larger sample numbers and the detection of additional polymorphisms that affect gene expression are needed before we can conclude that NMDA receptor expression and serum levels Of D-serine, if involved in schizophrenia pathophysiology, are independent and additive events. (c) 2005 Elsevier Ireland Ltd. All rights reserved.