More evidence supports the association of PPP3CC with schizophrenia

Liu, Y L; Fann, Cathy S.J.; Liu, C M; Chang, Chien-Ching; Yang, Wen-Jen; Chung, Wen‐Hung; Yu, Sung-Liang; Hwang, Tzung‐Jeng; Hsieh, Ming H.; Tsuang, Ming-Ming; Wu, Jer‐Yuarn; Jou, Yuh–Shan; Faraone, Stephen V.; Tsuang, Ming T.; Chen, Wei-Jen

doi:10.1038/sj.mp.4001977

Cited by 56 publications

(40 citation statements)

References 46 publications

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“…In contrast to most other tissues, parts of the brain produce the CnA␥ isoform. The gene encoding this isoform has been named a candidate susceptibility gene for schizophrenia, because singlenucleotide polymorphisms within and near this gene have been associated with schizophrenia in different ethnic groups (18,19 ).…”

Section: Brainmentioning

confidence: 99%

Molecular Diagnostics of Calcineurin-Related Pathologies

Musson

Cobbaert²,

Smit³

2012

Clinical Chemistry

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BACKGROUND The Ca2+-dependent protein phosphatase enzyme calcineurin (Cn) (protein phosphatase 3) is best known for its role as director of the adaptive immune response. One of its principal substrates is the nuclear factor of activated T cells (NFAT), which translocates to the nucleus after dephosphorylation to mediate gene transcription. Drugs targeting Cn (the Cn inhibitors tacrolimus and cyclosporin A) have revolutionized posttransplantation therapy in allograft recipients by considerably reducing rejection rates. CONTENT Owing primarily to intensive study of the side effects of the Cn inhibitors, the unique importance of Cn and Cn/NFAT signaling in the normal physiological processes of many other cell and tissue types is becoming more evident. During the last decade, it has become clear that an extensive and diverse array of clinical conditions can be traced back, at least in part, to a disturbed Cn-signaling axis. Hence, both diagnostics and therapeutic monitoring could benefit from a technique that conveniently reads out Cn/NFAT operative status. SUMMARY This review outlines the current knowledge on the pathologic conditions that have calcineurin as a common denominator and reports on the progress that has been made toward successfully applying Cn and Cn/NFAT activity markers in molecular diagnostics.

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Section: Brainmentioning

confidence: 99%

Molecular Diagnostics of Calcineurin-Related Pathologies

Musson

Cobbaert²,

Smit³

2012

Clinical Chemistry

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“…24 However, only a few microarray analysis using immortalized lymphocytes from patients with schizophrenia have been reported. [25][26][27] Whether immortalized lymphocytes are an appropriate alternative to neuronal tissue remains controversial.…”

Section: Introductionmentioning

confidence: 99%

Dysbindin-1 and NRG-1 gene expression in immortalized lymphocytes from patients with schizophrenia

et al. 2011

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The dysbindin-1 and neuregulin-1 (NRG-1) genes are related to schizophrenia. Expression studies in postmortem brains have revealed lower expression of dysbindin-1 and higher expression of NRG-1 in brain tissue from subjects with schizophrenia. In addition to the difficulty of sampling, the use of postmortem brain tissues is not ideal because these tissues are heterogeneous with respect to biochemical parameters, lifetime history of medications and physiological status at the time of death. In contrast, medication and environmental influences that could mask the genetic basis of differences in RNA expression are removed in immortalized lymphocytes by culturing. Only a few microarray analysis studies using immortalized lymphocytes in schizophrenia have been reported, and whether immortalized lymphocytes are an appropriate alternative to neuronal tissue remains controversial. In this study, we measured the mRNA expression levels of dysbindin-1, NRG-1 and two other genes (NPY1R and GNAO1) in immortalized lymphocytes from 45 patients with schizophrenia and 45 controls using real-time quantitative reverse transcriptase-PCR. No difference was observed between patients and controls with respect to the expression of dysbindin-1, NRG-1, NPY1R or GNAO1 gene. Our findings suggest that the gene expression profile of immortalized lymphocyte from schizophrenic patients is different from that in postmortem brain tissue at least with respect to the dysbindin-1 and NRG-1 genes. Journal of Human Genetics INTRODUCTIONSchizophrenia is a complex genetic disorder that is characterized by profound disturbances of cognition, emotion and social functioning. It affects B1% of the general population world wide. The dysbindin-1 and neuregulin-1 (NRG-1) genes are related to schizophrenia, 1 and the dysbindin-1 gene is also associated with cognitive functions. [2][3][4] Furthermore, the Sandy mouse, which expresses no dysbindin-1, has been reported to have behavioral abnormalities, cognitive deficits and a synaptic dysfunction that is related to the pathophysiology of schizophrenia. [5][6][7] Identified risk variants of NRG-1 are associated with the reduced white matter volume that is observed in schizophrenic brains. 8 The NRG-1 gene spans 1.2 Mb 9 and gives rise to many structurally and functionally distinct isoforms, through alternative promoter usage. These isoforms are divided into three classic groups: 10 type I (previously known as acetylcholine receptor inducing activity, heregulin or neu differentiation factor), type II (glia growth factor) and type III (cysteine-rich domain containing), which are based on distinct amino termini. Additional NRG-1 5¢ exons have

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“…1-4 Numerous family-based linkage or population-based studies have identified a large set of schizophrenia-associated loci; however, many have not been replicated either in a different ethnic background, 5,6 or in the same ethnic background but in a diverse geographical location. 7,8 Although the number of risk loci is rather large, only a small portion overlaps with the large cumulative pool of genes that have shown changes of expression in the disease state. This suggests a heavily weighted portion of the functionally affected genes in schizophrenia that is unlikely to result directly from the susceptibility loci.…”

Section: Introductionmentioning

confidence: 99%

An integrated genomic analysis of gene-function correlation on schizophrenia susceptibility genes

Chu

Liu

2010

J Hum Genet

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Schizophrenia is a highly complex inheritable disease characterized by numerous genetic susceptibility elements, each contributing a modest increase in risk for the disease. Although numerous linkage or association studies have identified a large set of schizophrenia-associated loci, many are controversial. In addition, only a small portion of these loci overlaps with the large cumulative pool of genes that have shown changes of expression in schizophrenia. Here, we applied a genomic gene-function approach to identify susceptibility loci that show direct effect on gene expression, leading to functional abnormalities in schizophrenia. We carried out an integrated analysis by cross-examination of the literature-based susceptibility loci with the schizophrenia-associated expression gene list obtained from our previous microarray study (Journal of Human Genetics (2009) 54: 665-75) using bioinformatic tools, followed by confirmation of gene expression changes using qPCR. We found nine genes (CHGB, SLC18A2, SLC25A27, ESD, C4A/C4B, TCP1, CHL1 and CTNNA2) demonstrate gene-function correlation involving: synapse and neurotransmission; energy metabolism and defense mechanisms; and molecular chaperone and cytoskeleton. Our findings further support the roles of these genes in genetic influence and functional consequences on the development of schizophrenia. It is interesting to note that four of the nine genes are located on chromosome 6, suggesting a special chromosomal vulnerability in schizophrenia.

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More evidence supports the association of PPP3CC with schizophrenia

Cited by 56 publications

References 46 publications

Molecular Diagnostics of Calcineurin-Related Pathologies

Molecular Diagnostics of Calcineurin-Related Pathologies

Dysbindin-1 and NRG-1 gene expression in immortalized lymphocytes from patients with schizophrenia

An integrated genomic analysis of gene-function correlation on schizophrenia susceptibility genes

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