國家衛生研究院 NHRI:Item 3990099045/4911
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    題名: Resequencing of the vesicular glutamate transporter 2 gene (VGLUT2) reveals some rare genetic variants that may increase the genetic burden in schizophrenia
    作者: Shen, YC;Liao, DL;Lu, CL;Chen, JY;Liou, YJ;Chen, TT;Chen, CH
    貢獻者: Division of Mental Health and Addiction Medicine
    摘要: Objectives: Vesicular glutamate transporters (VGLUT1-3) package glutamate into vesicles in the presynaptic terminal and regulate the release of glutamate. In mesencephalic dopamine neuron culture, the majority of isolated dopamine neurons express VGLUT2, but not VGLUT1 or 3, have been demonstrated. As related to the dysregulated glutamatergic hypothesis of schizophrenia, the gene encoding VGLUT2 is the most plausible candidate involved in the pathogenesis of this illness. Methods: We searched for genetic variants in the promoter region and 12 exons (including UTR ends) of the VGLUT2 gene using direct sequencing in a sample of Han Chinese schizophrenic patients (n = 375) and non-psychotic controls (n = 366) from Taiwan, and conducted a case-control association study. Results: We identified 8 common SNPs in the VGLUT2 gene. SNP and haplotype-based analyses showed no association with schizophrenia. Besides, we identified 9 rare variants in 13 out of 375 patients, including 3 variants located at the promoter region, 2 synonymous variants located at protein coding regions, and 4 variants located at UTR ends. No rare variants were found in the control subjects. Collectively, these rare variants were significantly overrepresented in the patient group (3.5% versus 0, p value of Fisher's exact test = 2.3 ? 10<sup>- 5</sup>), suggesting they may contribute to the pathogenesis of schizophrenia. Conclusion: Although the functional significance of these rare variants remains to be characterized, our study may lend support to the multiple rare mutations hypothesis of schizophrenia, and may provide genetic clues to indicate the involvement of the glutamate transmission pathway in the pathogenesis of schizophrenia.
    日期: 2010-08
    關聯: Schizophrenia Research. 2010 Aug;121(1-3):179-186.
    Link to: http://dx.doi.org/10.1016/j.schres.2010.05.015
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0920-9964&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000281073700021
    Cited Times(Scopus): http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=77955055746
    顯示於類別:[陳嘉祥(2009-2013)] 期刊論文
    [廖定烈(2005-2008)] 期刊論文

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