Kunugi H, Ishida S, Akahane A, Nanko S
Department of Psychiatry, Teikyo University School of Medicine 11-1, Kaga 2 Chome, Itabashi-ku, Tokyo, 173-8605, Japan.
Mol Psychiatry. 2001 Jul;6(4):456-60. doi: 10.1038/sj.mp.4000895.
The synaptic vesicular monoamine transporter (SVMT), alternatively vesicular monoamine transporter 2 (VMAT2), pumps cytosolic monoamines including dopamine, norepinephrine, serotonin, and histamine into synaptic vesicles. Altered functions of SVMT have been implicated in the pathogensis of several neuropsychiatric diseases. We determined exon/intron boundaries of the human SVMT gene and performed mutational analysis for the exonic and neighboring intronic regions of the gene. Detected polymorphisms were subject to association analysis with schizophrenia in a family-based design. The human SVMT gene consists, of 16 exons and 15 introns, which is consistent with the murine SVMT gene. When mutational analysis was performed by the single strand conformational polymorphism (SSCP) analysis, we found two and four single nucleotide polymorphisms (SNPs) in exons and neighboring introns, respectively. Neither exonic SNP results in an amino acid change. In family-based association analyses in a sample of 50 Japanese schizophrenics and their parents, no significant association was found for the intronic polymorphisms. Our data suggest that there is no common polymorphism in the SVMT gene affecting the primary structure of the human SVMT protein. Furthermore, we obtained no evidence for the major effect of the novel polymorphisms on susceptibility to schizophrenia.
突触囊泡单胺转运体（SVMT），又称囊泡单胺转运体2（VMAT2），可将包括多巴胺、去甲肾上腺素、5-羟色胺和组胺在内的胞质单胺泵入突触囊泡。SVMT功能改变与多种神经精神疾病的发病机制有关。我们确定了人类SVMT基因的外显子/内含子边界，并对该基因的外显子和相邻内含子区域进行了突变分析。检测到的多态性在基于家系的设计中与精神分裂症进行关联分析。人类SVMT基因由16个外显子和15个内含子组成，这与小鼠SVMT基因一致。当通过单链构象多态性（SSCP）分析进行突变分析时，我们分别在外显子和相邻内含子中发现了两个和四个单核苷酸多态性（SNP）。外显子SNP均未导致氨基酸变化。在对50名日本精神分裂症患者及其父母的样本进行的基于家系的关联分析中，未发现内含子多态性与精神分裂症有显著关联。我们的数据表明，SVMT基因中不存在影响人类SVMT蛋白一级结构的常见多态性。此外，我们没有获得新多态性对精神分裂症易感性有主要影响的证据。
