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

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.

• Authors: Chihiro Kakiuchi, Mizuho Ishiwata, Shinichiro Nanko, Norio Ozaki, Nakao Iwata, Tadashi Umekage, Mamoru Tochigi, Kazuhisa Kohda, Tsukasa Sasaki, Akira Imamura, Yuji Okazaki, Tadafumi Kato
• Journal: American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics (Am J Med Genet B Neuropsychiatr Genet) Vol. 147B Issue 5 Pg. 557-64 (Jul 05 2008) ISSN: 1552-485X [Electronic] United States
• PMID: 18081029 (Publication Type: Case Reports, Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright 2007 Wiley-Liss, Inc.

Chemical References

• ADM protein, human
• Selenoproteins
• Adrenomedullin
• Methionine Sulfoxide Reductases

Topics

• Adrenomedullin (biosynthesis, genetics)
• Adult
• Case-Control Studies
• Cells, Cultured
• Female
• Gene Dosage
• Gene Expression Profiling
• Humans
• Lymphocyte Subsets (metabolism, pathology)
• Male
• Methionine Sulfoxide Reductases (biosynthesis, genetics)
• Middle Aged
• Oligonucleotide Array Sequence Analysis
• Pregnancy
• Schizophrenia (genetics, metabolism, pathology)
• Selenoproteins (biosynthesis, genetics)
• Twins, Monozygotic (genetics, psychology)
• Up-Regulation (physiology)