| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2004: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2003: ¥2,600,000 (Direct Cost: ¥2,600,000)
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| Research Abstract |
Recently atypical antipsychotics are widely used for treatment of schizophrenia. Although it is well known that these drugs frequently induce adverse effects, such as glucose intolerance, hyperlipidemia, and obesity, the mechanism of these adverse effects has not been clearly elucidated.
In this study, we investigated the relationship between these side effects and genetic markers in schizophrenic patients treated with atypical antipsychotics, olanzapine or perospirone, in order to develop how to predict these adverse effects in schizophrenic patients with olanzapine and perospirone.
So far, we have collected blood samples and clinical data from 50 schizophrenic patients. We have analyzed the association between side effects such as glucose intolerance, obesity and genetic marker such as dopamine D2 receptor polymorphisms (Taq1A,-141 Ins/Del), beta2 adrenergic receptor polymorphisms (Arg16Gly,Gln27Glu), and beta3 adrenergic receptor polymorphism (Trp64Arg).
A patient, who developed diabetes mellitus during the treatment with perospirone and showed absence of Gly16 mutated allele on beta2 adrenergic receptor which has been regarded as decreasing the risk of diabetes.
Also there was a patient who developed extremely remarkable weight gain while he was treated with olanzapine. The cause is unknown at this point, but it is considered very important to explore the causal genetic factor in such a patient.
Further studies involving larger patient numbers and systematic pharmacogenomic analyses are worthwhile to obtain clinically useful genetic background, with regard to glucose intolerance, hyperlipidemia, and obesity.
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