Genetic and functional analysis of the DLG4 gene encoding the post-synaptic density protein 95 in schizophrenia.

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...

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Autores principales:	Min-Chih Cheng, Chao-Lin Lu, Sy-Ueng Luu, Ho-Min Tsai, Shih-Hsin Hsu, Tzu-Ting Chen, Chia-Hsiang Chen
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2010
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/3ece60630b394a5bac0f92eb316f1499
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spelling	oai:doaj.org-article:3ece60630b394a5bac0f92eb316f14992021-11-18T07:02:10ZGenetic and functional analysis of the DLG4 gene encoding the post-synaptic density protein 95 in schizophrenia.1932-620310.1371/journal.pone.0015107https://doaj.org/article/3ece60630b394a5bac0f92eb316f14992010-12-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21151988/?tool=EBIhttps://doaj.org/toc/1932-6203Hypofunction 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.Min-Chih ChengChao-Lin LuSy-Ueng LuuHo-Min TsaiShih-Hsin HsuTzu-Ting ChenChia-Hsiang ChenPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 5, Iss 12, p e15107 (2010)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Min-Chih Cheng Chao-Lin Lu Sy-Ueng Luu Ho-Min Tsai Shih-Hsin Hsu Tzu-Ting Chen Chia-Hsiang Chen Genetic and functional analysis of the DLG4 gene encoding the post-synaptic density protein 95 in schizophrenia.
description	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.
format	article
author	Min-Chih Cheng Chao-Lin Lu Sy-Ueng Luu Ho-Min Tsai Shih-Hsin Hsu Tzu-Ting Chen Chia-Hsiang Chen
author_facet	Min-Chih Cheng Chao-Lin Lu Sy-Ueng Luu Ho-Min Tsai Shih-Hsin Hsu Tzu-Ting Chen Chia-Hsiang Chen
author_sort	Min-Chih Cheng
title	Genetic and functional analysis of the DLG4 gene encoding the post-synaptic density protein 95 in schizophrenia.
title_short	Genetic and functional analysis of the DLG4 gene encoding the post-synaptic density protein 95 in schizophrenia.
title_full	Genetic and functional analysis of the DLG4 gene encoding the post-synaptic density protein 95 in schizophrenia.
title_fullStr	Genetic and functional analysis of the DLG4 gene encoding the post-synaptic density protein 95 in schizophrenia.
title_full_unstemmed	Genetic and functional analysis of the DLG4 gene encoding the post-synaptic density protein 95 in schizophrenia.
title_sort	genetic and functional analysis of the dlg4 gene encoding the post-synaptic density protein 95 in schizophrenia.
publisher	Public Library of Science (PLoS)
publishDate	2010
url	https://doaj.org/article/3ece60630b394a5bac0f92eb316f1499
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Genetic and functional analysis of the DLG4 gene encoding the post-synaptic density protein 95 in schizophrenia.

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