TY - JOUR
T1 - Up-regulation of ADM and SEPX1 in the lymphoblastoid cells of patients in monozygotic twins discordant for schizophrenia
AU - Kakiuchi, Chihiro
AU - Ishiwata, Mizuho
AU - Nanko, Shinichiro
AU - Ozaki, Norio
AU - Iwata, Nakao
AU - Umekage, Tadashi
AU - Tochigi, Mamoru
AU - Kohda, Kazuhisa
AU - Sasaki, Tsukasa
AU - Imamura, Akira
AU - Okazaki, Yuji
AU - Kato, Tadafumi
PY - 2008/7/5
Y1 - 2008/7/5
N2 - 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.
AB - 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.
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U2 - 10.1002/ajmg.b.30643
DO - 10.1002/ajmg.b.30643
M3 - Article
C2 - 18081029
AN - SCOPUS:46949092428
SN - 1552-4841
VL - 147
SP - 557
EP - 564
JO - American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics
JF - American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics
IS - 5
ER -
