Differential RNA expression between schizophrenic patients and controls of the dystrobrevin binding protein 1 and neuregulin 1 genes in immortalized lymphocytes.
The dystrobrevin binding protein 1 (DTNBP1) and neuregulin 1 (NRG1) genes have been related to schizophrenia (SZ) and bipolar disorder (BP) by several whole-genome linkage and associations studies. Few expression studies in post-mortem brains have also reported a lower or a higher expression of DTNBP1 and NRG1, respectively, in SZ. Since the difficulty to access post-mortem brains, we evaluated RNA expression of DTNBP1 and NRG1 in immortalized lymphocytes of SZ patients and unrelated-family controls. An antipsychotic stimulation was also used to challenge the genetic background of the subjects and enhance differential expression. Immortalized lymphocytes of twelve SZ and twelve controls were grown individually in the presence or not of the antipsychotic olanzapine (Zyprexa; EliLilly). RNA was extracted and pooled in four groups of three SZ and four groups of three controls, and used to probe Agilent 18K microchips. Mean gene expression values were contrasted between SZ and control groups using a T-test. For DTNBP1, RNA expression was lower in SZ than in controls before (-28%; p=0.02) and after (-30%; p=0.01) olanzapine stimulation. Similarly, NRG1 GGF2 isoform showed a lower expression in SZ before (-29%; p=0.04) and after (-33%; p=0.02) olanzapine stimulation. In contrast, NRG1 GGF isoform showed no significant difference between SZ and controls (-7%; p=0.61, +3%; p=0.86, respectively), but was slightly repressed by olanzapine in controls (-8%; p=0.008) but not in SZ (+1%; p=0.91). These results are in agreement with those observed in post-mortem brain when the isoforms involved are considered.
Chagnon
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YC
Laval University Research Center Robert-Giffard, Québec, Québec, Canada. Yvon.Chagnon@crulrg.ulaval.ca
Roy
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MA
Bureau
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Mérette
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Maziade
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D000328:Adult; D000368:Aged; D014150:Antipsychotic Agents / Q000494:pharmacology / Q000627:therapeutic use; D001569:Benzodiazepines / Q000494:pharmacology / Q000627:therapeutic use; D001714:Bipolar Disorder / Q000235:genetics / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism; D002478:Cells, Cultured; D035061:Control Groups; D000074765:Dysbindin; D049029:Dystrophin-Associated Proteins; D005260:Female; D015870:Gene Expression; D006801:Humans; D008214:Lymphocytes / Q000378:metabolism*; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D020890:Neuregulin-1 / Q000235:genetics* / Q000378:metabolism; D000077152:Olanzapine; D010597:Pharmacogenetics; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D012313:RNA / Q000235:genetics / Q000378:metabolism; D012559:Schizophrenia / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism
D014150:Antipsychotic Agents; D002352:Carrier Proteins; C432416:DTNBP1 protein, human; D000074765:Dysbindin; D049029:Dystrophin-Associated Proteins; C094131:NRG1 protein, human; D009419:Nerve Tissue Proteins; D020890:Neuregulin-1; D020033:Protein Isoforms; D001569:Benzodiazepines; D012313:RNA; D000077152:Olanzapine