Proteomic Analysis of Lymphoblastoid Cells Derived from Monozygotic Twins Discordant for Bipolar Disorder: A Preliminary Study

Kazuno, An‐a; Ohtawa, Kenji; Otsuki, Kaori; Usui, Masaya; Sugawara, Hiroko; Okazaki, Yuji; Kato, Takeshi

doi:10.1371/journal.pone.0053855

Cited by 27 publications

(16 citation statements)

References 51 publications

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“…RPLP0 was identified as the most optimal housekeeping gene in human blood CD4 + T cells derived from asthmatics with or without depression (Wang et al, ). Additionally, it is found that RPLP0 is down‐regulated in bipolar disorder (Kazuno et al, ). In the present study, we found that RPLP0 was down‐regulated, which suggested the crucial role of RPLP0 in the development of MDD.…”

Section: Discussionmentioning

confidence: 99%

Seeking for potential pathogenic genes of major depressive disorder in the Gene Expression Omnibus database

Feng¹,

Zhou²,

Gao³

et al. 2019

Asia-Pacific Psychiatry

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Introduction: Major depressive disorder (MDD) is one of the most common mental disorders worldwide. The aim of this study was to identify potential pathological genes in MDD. Methods: We searched and downloaded gene expression data from the Gene Expression Omnibus database to identify differentially expressed genes (DEGs) in MDD. Then, Kyoto Encyclopedia of Genes and Genomes pathway, Gene Ontology analysis, and protein-protein interaction (PPI) network were applied to investigate the biological function of identified DEGs. The quantitative real-time polymerase chain reaction and a published dataset were used to validate the result of bioinformatics analysis. Results: A total of 514 DEGs were identified in MDD. In the PPI network, some hub genes with high degrees were identified, such as EEF2, RPL26L1, RPLP0, PRPF8, LSM3, DHX9, RSRC1, and AP2B1. The result of in vitro validation of RPL26L1, RSRC1, TOMM20L, RPLPO, PRPF8, AP2B1, STIP1, and C5orf45 was consistent with the bioinformatics analysis. Electronic validation of C5orf45, STIP1, PRPF8, AP2B1, and SLC35E1 was consistent with the bioinformatics analysis. Discussion: The deregulated genes could be used as potential pathological factors of MDD. In addition, EEF2, RPL26L1, RPLP0, PRPF8, LSM3, DHX9, RSRC1, and AP2B1 might be therapeutic targets for MDD. K E Y W O R D S drug target, gene expression, in vitro validation, major depressive disorder, protein-protein interaction network

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Section: Discussionmentioning

confidence: 99%

Seeking for potential pathogenic genes of major depressive disorder in the Gene Expression Omnibus database

Feng¹,

Zhou²,

Gao³

et al. 2019

Asia-Pacific Psychiatry

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“…Of note, our finding of upregulation of just one gene in primary analysis, the PGAM1 , in bipolar disorder patients compared with healthy control subjects mirrored previous findings in lymphoblastoid cells. 19 …”

Section: Discussionmentioning

confidence: 99%

A composite peripheral blood gene expression measure as a potential diagnostic biomarker in bipolar disorder

et al. 2015

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Gene expression in peripheral blood has the potential to inform on pathophysiological mechanisms and has emerged as a viable avenue for the identification of biomarkers. Here, we aimed to identify gene expression candidate genes and to explore the potential for a composite gene expression measure as a diagnostic and state biomarker in bipolar disorder. First, messenger RNA levels of 19 candidate genes were assessed in peripheral blood mononuclear cells of 37 rapid cycling bipolar disorder patients in different affective states (depression, mania and euthymia) during a 6–12-month period and in 40 age- and gender-matched healthy control subjects. Second, a composite gene expression measure was constructed in the first half study sample and independently validated in the second half of the sample. We found downregulation of POLG and OGG1 expression in bipolar disorder patients compared with healthy control subjects. In patients with bipolar disorder, upregulation of NDUFV2 was observed in a depressed state compared with a euthymic state. The composite gene expression measure for discrimination between patients and healthy control subjects on the basis of 19 genes generated an area under the receiver-operating characteristic curve of 0.81 (P<0.0001) in sample 1, which was replicated with a value of 0.73 (P<0.0001) in sample 2, corresponding with a moderately accurate test. The present findings of altered POLG, OGG1 and NDUFV2 expression point to disturbances within mitochondrial function and DNA repair mechanisms in bipolar disorder. Further, a composite gene expression measure could hold promise as a potential diagnostic biomarker.

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“…Such biomarkers, when validated across cohorts, will also have an important economic impact, with emphasis changing from treatment to detection and prevention. To reach this goal, other epigenetic marks need to be analysed in the same way as DNA methylation and integrated with other ‘omics' such as metabolomics [93,94], proteomics [95] and metagenomics [96]. …”

Section: Discussionmentioning

confidence: 99%

Epigenetics in Twin Studies

Craig

2013

Med Epigenet

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It is emerging that the environment, particularly in early life, can cause long-lasting epigenetic changes that are accompanied by latent effects on health outcomes. Furthermore, the reversibility of some epigenetic marks in animal models indicates that, once recognised in early life, such epigenetic changes may be reversible, providing potential avenues for disease prognosis, prevention and treatment. Twin studies, which were originally used to calculate gross components of genetic and environmental influence on phenotype, are now being used to associate specific genetic and epigenetic variants with specific human conditions and diseases. Epigenome-wide association studies of phenotypically discordant, genetically ‘identical' monozygotic twins have the power to focus solely on epigenetic association with disease and are providing information about gene-environment interaction and variable penetrance. Going beyond association, such studies can help generate epigenetic biomarkers to predict disease long before clinical onset, which has important implications for disease prevention. Furthermore, when epigenetic information on a genome scale is combined with other ‘omics', twin studies will be a strong force for the improvement of human health.

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Proteomic Analysis of Lymphoblastoid Cells Derived from Monozygotic Twins Discordant for Bipolar Disorder: A Preliminary Study

Cited by 27 publications

References 51 publications

Seeking for potential pathogenic genes of major depressive disorder in the Gene Expression Omnibus database

Seeking for potential pathogenic genes of major depressive disorder in the Gene Expression Omnibus database

A composite peripheral blood gene expression measure as a potential diagnostic biomarker in bipolar disorder

Epigenetics in Twin Studies

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