Polymorphism analysis of the upstream region of the human N-methyl-d-aspartate receptor subunit NR1 gene (GRIN1): implications for schizophrenia
Polymorphism analysis of the upstream region of the human N-methyl-d-aspartate receptor subunit NR1 gene (GRIN1): implications for schizophrenia
复制标题
DOI：
10.1016/s0920-9964(02)00161-5
复制
发表时间：
2002-11
影响因子：
4.5
通讯作者：
Ayako Tani;Rumiko Kikuta;Kanako Itoh;A. Joo;H. Shibata;H. Ninomiya;N. Tashiro;Y. Fukumaki
中科院分区：
文献类型：
--
作者：
Ayako Tani;Rumiko Kikuta;Kanako Itoh;A. Joo;H. Shibata;H. Ninomiya;N. Tashiro;Y. Fukumaki
N-甲基-d-天冬氨酸（NMDA）受体（GRIN 1）NR 1亚基基因功能障碍与精神分裂症的发病机制有关。支持这一假设的是行为异常，让人联想到精神分裂症的小鼠与衰减的NR 1亚单位受体的表达和NR 1 mRNA水平降低，在死后的大脑中的精神分裂症患者。我们筛选了GRIN 1翻译起始密码子上游+51和-941之间的单核苷酸多态性（SNP），并确定了17个SNP，其中10个位于包含Sp1基序和GSG基序的区域内。由于191-196名日本精神分裂症患者和202-216名对照的基因分型显示精神分裂症与GRIN 1上游区域的SNPs之间没有显著关联，因此这些SNPs显然在日本人群的精神分裂症发病机制中不起关键作用。
Dysfunction of the gene for the NR1 subunit of the N-methyl-d-aspartate (NMDA) receptor (GRIN1) has been implicated in the pathogenesis of schizophrenia. In support of this hypothesis are behavioral abnormalities reminiscent of schizophrenia in mice with an attenuated expression of the NR1 subunit receptor and the reduced level of NR1 mRNA in postmortem brains of patients with schizophrenia. We screened single nucleotide polymorphisms (SNPs) in the upstream region between +51 and −941 from the translation initiation codon of GRIN1 and identified 17 SNPs, 10 of which were located within the region containing the Sp1 motif and the GSG motifs. As genotyping of 191–196 Japanese patients with schizophrenia and 202–216 controls revealed no significant association between schizophrenia and the SNPs in the upstream region of GRIN1, these SNPs apparently do not play a critical role in the pathogenesis of schizophrenia in the Japanese population.