A search for glucose intolerance related gene associated with atypical antipsychotics-induced adverse effects

近年来，非典型抗精神病药物被广泛应用于精神分裂症的治疗。虽然众所周知，这些药物经常引起不良反应，如葡萄糖耐受不良、高脂血症和肥胖，但这些不良反应的机制尚未清楚阐明。本研究旨在探讨非典型抗精神病药物奥氮平或螺环酮治疗精神分裂症患者的这些不良反应与遗传标记的关系，以探讨如何预测奥氮平和螺环酮治疗精神分裂症患者的这些不良反应。到目前为止，我们已经收集了50名精神分裂症患者的血液样本和临床数据。我们分析了葡萄糖耐受不良、肥胖等副作用与遗传标记（如多巴胺D2受体多态性（Taq1A,-141 Ins/Del）、β 2肾上腺素能受体多态性（Arg16Gly,Gln27Glu）和β 3肾上腺素能受体多态性（Trp64Arg））之间的关系。患者在使用螺环酮治疗期间发生糖尿病，β 2肾上腺素能受体Gly16突变等位基因缺失，被认为可降低糖尿病风险。还有一个病人在接受奥氮平治疗期间体重显著增加。病因目前尚不清楚，但在这种患者中探索病因遗传因素是非常重要的。进一步的研究涉及更大的患者数量和系统的药物基因组学分析，对于获得关于葡萄糖耐受不良、高脂血症和肥胖的临床有用的遗传背景是值得的。

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.