國家衛生研究院 NHRI:Item 3990099045/1424
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    题名: Association of missense variants of the PRKC, apoptosis, WT1, regulator (PAWR) gene with schizophrenia
    作者: Wang, LH;Chen, JY;Liou, YJ;Wang, YC;Lai, IC;Liao, DL;Chen, CH
    贡献者: Division of Mental Health and Substance Abuse Research
    摘要: Abnormal dopamine signal transduction is implicated in the pathophysiology of schizophrenia. A recent study showed that prostate apoptosis response 4 protein (Par-4) interacts with dopamine D2 receptor and plays an important role in dopamine signaling. Par-4 knockout mice showed depression-like behavior, suggesting that Par-4 gene may be associated with mental disorders in human. The study was aimed to determine whether the PRKC, apoptosis, WT1, regulator gene (PAWR) that encodes the human homolog of Par-4 protein is a susceptibility gene for schizophrenia. We systematically screened for mutations at the 5' untranslated region (5'UTR) and all the exonic regions of the PAWR gene in a sample of Han Chinese schizophrenic patients from Taiwan. We identified two missense single nucleotide polymorphisms (SNPs) that are in strong linkage in our sample (D'=0.98), i.e. P78R at exon 2 and I199M at exon 3, respectively. SNP- and haplotype-based analysis showed that these two variants are associated with schizophrenia; there is an overrepresentation of RR homozygotes of P78R (OR=2.00, 95% CI= 1.05-3.83) and MM homozygotes of I199M (OR = 1.81, 95% CI = 0.95-3.54) in schizophrenic patients as compared to control subjects. When subjects were divided by gender, the association is specifically with female patients (OR=2.94 for RR and OR=2.7 for MM), but not with male patients. Our results indicate that the PAWR gene is associated with schizophrenia in our population, and this study provides genetic evidence to support the dopamine hypothesis of schizophrenia. (c) 2008 Elsevier Inc. All rights reserved.
    关键词: Clinical Neurology;Neurosciences;Pharmacology & Pharmacy;Psychiatry
    日期: 2008-04-01
    關聯: Progress in Neuro-Psychopharmacology and Biological Psychiatry. 2008 Apr;32(3):870-875.
    Link to: http://dx.doi.org/10.1016/j.pnpbp.2008.01.003
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0278-5846&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000254690300037
    Cited Times(Scopus): http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=39749190721
    显示于类别:[陳嘉祥(2009-2013)] 期刊論文
    [廖定烈(2005-2008)] 期刊論文

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