P-1104 - The effect of clozapine on the expression of obesity genes - 13/06/12
Résumé |
Clozapine is a second generation antipsychotic drug that is often used for treatment of schizophrenia. Although clozapine does not produce extrapyramidal side effects, it is well documented that it often causes a substantial increase in body weight among the patients who have received the treatment. This is a major issue in antipsychotic medication of schizophrenia as obesity is a risk factor for the development of type II diabetes, cardiovascular disease and certain types of cancer. The molecular mechanism that underlies this off-targeting effect has been poorly understood, but we hypothesize that the genes involved in obesity may play a role in developing clozapine-induced obesity. In this study, accordingly, we applied a human cell line (U937 cells) with quantitative PCR analysis to examine the effect of clozapine on the expression of obesity genes that were identified by genome-wide association study (GWAS). Our results revealed that expression of the neuronal growth regulator 1 (NEGR1) gene was significantly higher in U937 cells treated with clozapine concentrations of 0.5μg/ml (P=0.0165) and 1.0μg/ml (P=0.021), respectively, as compared with that in the vehicle-treated cells. This initial finding suggests that NEGR1 may be a target of clozapine, leading to the development of drug-induced obesity. The NEGR1 gene will be further investigated to determine its association with schizophrenia and to clarify what mechanism may be involved in its expression.
Le texte complet de cet article est disponible en PDF.Vol 27 - N° S1
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