國家衛生研究院 NHRI:Item 3990099045/5316
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    题名: Genetic and functional analysis of the DLG4 gene encoding the post-synaptic density protein 95 in schizophrenia
    作者: Cheng, MC;Lu, CL;Luu, SU;Tsai, HM;Hsu, SH;Chen, TT;Chen, CH
    贡献者: Division of Mental Health and Addiction Medicine
    摘要: Hypofunction of N-methyl-D-aspartate (NMDA) receptor-mediated signal transduction has been implicated in the pathophysiology of schizophrenia. Post-synaptic density protein 95 (PSD95) plays a critical role in regulating the trafficking and activity of the NMDA receptor and altered expression of the PSD95 has been detected in the post-mortem brain of patients with schizophrenia. The study aimed to examine whether the DLG4 gene that encodes the PSD95 may confer genetic susceptibility to schizophrenia. We re-sequenced the core promoter, all the exons, and 3' untranslated regions (UTR) of the DLG4 gene in 588 Taiwanese schizophrenic patients and conducted an association study with 539 non-psychotic subjects. We did not detect any rare mutations at the protein-coding sequences of the DLG4 gene associated with schizophrenia. Nevertheless, we identified four polymorphic markers at the core promoter and 5' UTR and one single nucleotide polymorphism (SNP) at the 3'UTR of the DLG4 gene in this sample. Genetic analysis showed an association of a haplotype (C-D) derived from 2 polymorphic markers at the core promoter (odds ratio = 1.26, 95% confidence interval = 1.06-1.51, p = 0.01), and a borderline association of the T allele of the rs13331 at 3'UTR with schizophrenia (odds ratio = 1.19, 95% confidence interval = 0.99-1.43, p = 0.06). Further reporter gene assay showed that the C-D-C-C and the T allele of the rs13331 had significant lower activity than their counter parts. Our data indicate that the expression of the DLG4 gene is subject to regulation by the polymorphic markers at the core promoter region, 5' and 3'UTR of the gene, and is associated with the susceptibility of schizophrenia.
    日期: 2010-12
    關聯: PLoS ONE. 2010 Dec;5(11):Article number e15107.
    Link to: http://dx.doi.org/10.1371/journal.pone.0015107
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=1932-6203&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000284868000024
    Cited Times(Scopus): http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=78649971622
    显示于类别:[陳嘉祥(2009-2013)] 期刊論文

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