國家衛生研究院 NHRI:Item 3990099045/6266
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    Please use this identifier to cite or link to this item: http://ir.nhri.org.tw/handle/3990099045/6266


    Title: Genetic and functional analysis of the gene encoding neurogranin in schizophrenia
    Authors: Shen, YC;Tsai, HM;Cheng, MC;Hsu, SH;Chen, SF;Chen, CH
    Contributors: Division of Mental Health and Addiction Medicine
    Abstract: OBJECTIVES: Schizophrenia is a highly heritable disorder, but many aspects of its etiology and pathophysiology remain poorly understood. Recently, a SNP rs12807809 located upstream of the neurogranin (NRGN) gene achieved genome-wide significance in this disorder. METHODS: In order to find the causal variants of NRGN gene in schizophrenia, we searched for genetic variants in the promoter region and all the exons (including both UTR ends and rs12807809) using direct sequencing in a sample of patients with schizophrenia (n=346) and non-psychotic controls (n=345), both being Han Chinese from Taiwan, and conducted an association and functional study. RESULTS: We identified 7 common polymorphisms in the NRGN gene. SNP and haplotype-based analyses displayed no associations with schizophrenia. Additionally, we identified 5 rare variants in 6 out of 346 patients, including 3 rare variants located at the promoter region (g.-620A>G, g.-578C>G, and g.-344G>A) and 2 rare variants located at 5' UTR (c.-74C>G, and c.-41G>A). No rare variants were found in the control subjects. The results of the reporter gene assay demonstrated that the regulatory activity of construct containing g.-620G, g.-578G, g.-344A, c.-74G, and c.-41A was significantly lower as compared to the wild type construct (P<0.01 for g.-578G; P<0.001 for the other constructs). In silico analysis also demonstrated their influences on the regulatory function of NRGN gene. CONCLUSIONS: Our study lends support to the hypothesis of multiple rare mutations in schizophrenia, and provides genetic clues that indicate the involvement of NRGN in this disorder.
    Date: 2012-05
    Relation: Schizophrenia Research. 2012 May;137(1-3):7-13.
    Link to: http://dx.doi.org/10.1016/j.schres.2012.01.011
    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:000303933800001
    Cited Times(Scopus): http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=84862795706
    Appears in Collections:[Chia-Hsiang Chen(2009-2013)] Periodical Articles

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