Genetic analysis of the calcineurin pathway identifies members of the EGR gene family, specifically EGR3, as potential susceptibility candidates in schizophrenia.

Genetic analysis of the calcineurin pathway identifies members of the EGR gene family, specifically EGR3, as potential susceptibility candidates in schizophrenia. Research Abstract Details 

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Genetic analysis of the calcineurin pathway identifies members of the EGR gene family, specifically EGR3, as potential susceptibility candidates in schizophrenia. Abstract Text:

Kazuo Yamada,David J Gerber,Yoshimi Iwayama,Tetsuo Ohnishi,Hisako Ohba,Tomoko Toyota,Jun Aruga,Yoshio Minabe,Susumu Tonegawa,Takeo Yoshikawa,

The calcineurin cascade is central to neuronal signal transduction, and genes in this network are intriguing candidate schizophrenia susceptibility genes. To replicate and extend our previously reported association between the PPP3CC gene, encoding the calcineurin catalytic gamma-subunit, and schizophrenia, we examined 84 SNPs from 14 calcineurin-related candidate genes for genetic association by using 124 Japanese schizophrenic pedigrees. Four of these genes (PPP3CC, EGR2, EGR3, and EGR4) showed nominally significant association with schizophrenia. In a postmortem brain study, EGR1, EGR2, and EGR3 transcripts were shown to be down-regulated in the prefrontal cortex of schizophrenic, but not bipolar, patients. These findings raise a potentially important role for EGR genes in schizophrenia pathogenesis. Because EGR3 is an attractive candidate gene based on its chromosomal location close to PPP3CC within 8p21.3 and its functional link to dopamine, glutamate, and neuregulin signaling, we extended our analysis by resequencing the entire EGR3 genomic interval and detected 15 SNPs. One of these, IVS1 + 607A-->G SNP, displayed the strongest evidence for disease association, which was confirmed in 1,140 independent case-control samples. An in vitro promoter assay detected a possible expression-regulatory effect of this SNP. These findings support the previous genetic association of altered calcineurin signaling with schizophrenia pathogenesis and identify EGR3 as a compelling susceptibility gene.

Genetic analysis of the calcineurin pathway identifies members of the EGR gene family, specifically EGR3, as potential susceptibility candidates in schizophrenia. Publishing Authors By Initials

K Yamada,DJ Gerber,Y Iwayama,T Ohnishi,H Ohba,T Toyota,J Aruga,Y Minabe,S Tonegawa,T Yoshikawa,

For similar mental disorders: schizophrenia and disorders with psychotic features: schizophrenia research abstracts see: mental disorders: schizophrenia and disorders with psychotic features: schizophrenia research

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Genetic analysis of the calcineurin pathway identifies members of the EGR gene family, specifically EGR3, as potential susceptibility candidates in schizophrenia. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Proceedings of the National Academy of Sciences of

VOLUME: 104

Page Numbers: 2815-20

Journal Abbreviation: Proc. Natl. Acad. Sci. U.S.A.

ISSN: 0027-8424

DAY: 20

MONTH: 02

YEAR: 2007

Genetic analysis of the calcineurin pathway identifies members of the EGR gene family, specifically EGR3, as potential susceptibility candidates in schizophrenia. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 7505876

Genetic analysis of the calcineurin pathway identifies members of the EGR gene family, specifically EGR3, as potential susceptibility candidates in schizophrenia. Keywords Mesh Terms:

KEYWORDS: Schizophrenia

MESH TERMS: genetics

Chemical & Substance for Abstract: Genetic analysis of the calcineurin pathway identifies members of the EGR gene family, specifically EGR3, as potential susceptibility candidates in schizophrenia. Information

Substance Name: Calcineurin

Registry Number: EC 3.1.3.-

Grant and Affiliation Information for Genetic analysis of the calcineurin pathway identifies members of the EGR gene family, specifically EGR3, as potential susceptibility candidates in schizophrenia.

AFFILIATION: Laboratories for Molecular Psychiatry, RIKEN Brain Science Institute, Saitama 351-0198, Japan.

Country: United States

AGENCY: United States NIMH

GRANT: P50 MH 58880

ACRONYM: MH

MEDLINETA: Proc Natl Acad Sci U S A

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