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，如葡萄糖耐量、高脂血症和肥胖，但这些不良反应的机制尚未明确。在这项研究中，我们调查了接受非典型抗精神病药物、奥氮平或培螺酮治疗的精神分裂症患者这些副作用与遗传标志物的关系，以开发如何预测服用奥氮平和培螺酮的精神分裂症患者的这些不良反应。我们分析了糖耐量异常、肥胖等副作用与遗传标记物如多巴胺D2受体多态(Taq1a，-141Ins/Del)、β2肾上腺素能受体多态(Arg16Gly，Gln27Glu)和β3肾上腺素能受体多态(Trp64Arg)之间的关系。一名患者在服用培螺酮期间发生糖尿病，并显示β2肾上腺素受体上的Gly16突变等位基因缺失，这被认为是降低糖尿病风险的。此外，还有一名患者在接受奥氮平治疗时体重显著增加。目前原因尚不清楚，但探索此类患者的致病遗传因素是非常重要的。进一步的研究涉及更多的患者数量和系统的药物基因组分析，值得获得临床上有用的遗传背景，如葡萄糖耐量减低、高脂血症和肥胖。

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.