Up-regulation of ADM and SEPX1 in the lymphoblastoid cells of patients in monozygotic twins discordant for schizophrenia

Chihiro Kakiuchi, Mizuho Ishiwata, Shinichiro Nanko, Norio Ozaki, Nakao Iwata, Tadashi Umekage, Mamoru Tochigi, Kazuhisa Kohda, Tsukasa Sasaki, Akira Imamura, Yuji Okazaki, Tadafumi Kato

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

The contribution of genetic factors to schizophrenia is well established and recent studies have indicated several strong candidate genes. However, the pathophysiology of schizophrenia has not been totally elucidated yet. To date, studies of monozygotic twins discordant for schizophrenia have provided insight into the pathophysiology of this illness; this type of study can exclude inter-individual variability and confounding factors such as effects of drugs. In this study we used DNA microarray analysis to examine the mRNA expression patterns in the lymphoblastoid (LB) cells derived from two pairs of monozygotic twins discordant for schizophrenia. From five independent replicates for each pair of twins, we selected five genes, which included adrenomedullin (ADM) and selenoprotein X1 (SEPX1), as significantly changed in both twins with schizophrenia. Interestingly, ADM was previously reported to be up-regulated in both the LB cells and plasma of schizophrenic patients, and SEPX1 was included in the list of genes up-regulated in the peripheral blood cells of schizophrenia patients by microarray analysis. Then, we performed a genetic association study of schizophrenia in the Japanese population and examined the copy number variations, but observed no association. These findings suggest the possible role of ADM and SEPX1 as biomarkers of schizophrenia. The results also support the usefulness of gene expression analysis in LB cells of monozygotic twins discordant for an illness.

Original languageEnglish
Pages (from-to)557-564
Number of pages8
JournalAmerican Journal of Medical Genetics, Part B: Neuropsychiatric Genetics
Volume147
Issue number5
DOIs
Publication statusPublished - 2008 Jul 5

Keywords

  • Adrenomedullin
  • DNA microarray
  • Gene expression
  • Genetic association study
  • Selenoprotein

ASJC Scopus subject areas

  • Genetics(clinical)
  • Psychiatry and Mental health
  • Cellular and Molecular Neuroscience

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    Kakiuchi, C., Ishiwata, M., Nanko, S., Ozaki, N., Iwata, N., Umekage, T., Tochigi, M., Kohda, K., Sasaki, T., Imamura, A., Okazaki, Y., & Kato, T. (2008). Up-regulation of ADM and SEPX1 in the lymphoblastoid cells of patients in monozygotic twins discordant for schizophrenia. American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics, 147(5), 557-564. https://doi.org/10.1002/ajmg.b.30643