Association of CYP2D6 polymorphisms and extrapyramidal symptoms in schizophrenia patients receiving risperidone: a retrospective study.
Association of CYP2D6 polymorphisms and extrapyramidal symptoms in schizophrenia patients receiving risperidone: a retrospective study.
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DOI：
10.1186/s40780-018-0126-y
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发表时间：
2018
影响因子：
1
通讯作者：
Yano I
中科院分区：
文献类型：
--
作者：
Ito T;Yamamoto K;Ohsawa F;Otsuka I;Hishimoto A;Sora I;Hirai M;Yano I
利培酮主要通过肝脏细胞色素P450 (CYP) 2D6代谢。编码CYP2D6的基因是高度多态性的。CYP2D6中间代谢物（IMs）的利培酮活性部分平均稳态血浆浓度高于广泛代谢物（EMs）。药物诱导的锥体外系症状量表（DIEPSS）评分与CYP2D6多态性之间的关联迄今尚未报道。本研究探讨了接受利培酮治疗的精神分裂症患者CYP2D6多态性与锥体外系症状严重程度的关系。接受利培酮治疗的精神分裂症患者被招募到神户大学医院进行研究。我们使用DIEPSS评估精神分裂症的锥体外系症状。CYP2D6*10和CYP2D6*14采用TaqMan®检测，CYP2D6*5采用长链pcr法检测。CYP2D6*1/*5、*1/*14、*5/*10、*10/*10、*10/*14为IMs， CYP2D6*1/*1、*1/*10为EMs。CYP2D6*5/*5、*5/*14、*14/*14的患者被归类为代谢不良者（PMs）。共有22名患者被纳入研究。没有患者被归类为PMs。利培酮剂量（mg/天）在EMs （n = 15）和IMs （n = 7）之间无显著差异(中位数四分位数范围：4.0 （2.0-6.0)vs. 4.0 (2.0-7.0) mg, p = 0.31）。精神分裂症患者的年龄和病程在两组间无显著差异。IMs组的DIEPSS评分显著高于EMs组(四分位数范围中位数：5.0 （3.5-6.5)vs. 0.0 (0.0 - 3.0), p < 0.001）。多元回归分析显示CYP2D6 IMs是DIEPSS的重要危险因素（p < 0.05）。在接受利培酮治疗的经鉴定为CYP2D6 IM的精神分裂症患者中，应特别注意锥体外系症状的发作。
Risperidone is mainly metabolized by cytochrome P450 (CYP) 2D6 in the liver. The gene encoding CYP2D6 is highly polymorphic. The average steady-state plasma concentration of risperidone active moiety is higher in the CYP2D6 intermediate metabolizers (IMs) compared with that in the extensive metabolizers (EMs). An association between drug-induced extrapyramidal symptoms scale (DIEPSS) score and CYP2D6 polymorphisms has not been reported to date. This study investigates the association of CYP2D6 polymorphisms with the severity of extrapyramidal symptoms in schizophrenia patients receiving risperidone therapy. Schizophrenia patients undergoing risperidone treatment were recruited for the study in the Kobe University Hospital. We evaluated extrapyramidal symptoms of schizophrenia using the DIEPSS. CYP2D6*10 and CYP2D6*14 were analyzed using TaqMan® assays, and CYP2D6*5 was analyzed using the long-PCR method. Patients with CYP2D6*1/*5, *1/*14, *5/*10, *10/*10, and *10/*14 were classified as IMs, and patients with CYP2D6*1/*1 and *1/*10 were classified as EMs. Patients with CYP2D6*5/*5, *5/*14, and *14/*14 were classified as poor metabolizers (PMs). A total of 22 patients were included in the study. No patients were classified as PMs. The dose of risperidone (mg/day) was not significantly different between EMs (n = 15) and IMs (n = 7) (median with the interquartile range: 4.0 (2.0–6.0) vs. 4.0 (2.0–7.0) mg, p = 0.31). The age and disease duration of schizophrenia were not significantly different between the EMs and IMs. The DIEPSS score in the IMs was significantly higher than that in the EMs (median with the interquartile range: 5.0 (3.5–6.5) vs. 0.0 (0.0–3.0), p < 0.001). The multiple regression analysis showed that CYP2D6 IMs is a significant risk factor for the DIEPSS (p < 0.05). Special attentions should be paid to the onset of extrapyramidal symptoms in schizophrenia patients identified as CYP2D6 IM undergoing risperidone therapy.