精神分裂症患者CYP2D6基因多态性与利培酮代谢的相关性研究  

Correlation between CYP2D6 polymorphism and risperidone metabolism in schizophrenic patients

作　　者：张婷[1] 饶庆敏 许莹[1] 杨梦心[1] 邱萍英[1] 林裕龙[1] Zhang Ting;Rao Qingmin;Xu Ying;Yang Mengxin;Qiu Pingying;Lin Yulong(Department of Laboratory Diagnosis, Brain Hospital Affiliated to Guangzhou Medical University, Guangzhou Huiai Hospital, Guangzhou 510170, China)

机构地区：[1]广州医科大学附属脑科医院广州市惠爱医院检验科,广州510170

出　　处：《中华检验医学杂志》2019年第4期306-311,共6页Chinese Journal of Laboratory Medicine

基　　金：广州市医学重点学科(2017-2019);广东省科技计划项目(2014A020212375)。

摘　　要：目的探讨精神分裂症患者CYP2D6等位基因多态性对利培酮(RISP)代谢的影响。方法实时荧光PCR分别检测120例连续服用RISP的精神分裂症患者CYP2D6*10、*4、*41以及*2的等位基因多态性。质谱分析法检测所有患者血液中RISP及其代谢产物9羟基-RISP(9-OH-RISP)的浓度。同时抽取部分样本对东方人群最常见的CYP2D6*10进行DNA测序。根据所检测的120例受检对象的基因型,将其分为3组,第1组为无携带影响CYP2D6酶活性等位基因的基因型,第2组为携带一个降低CYP2D6酶活性等位基因的基因型,第3组为携带两个降低CYP2D6酶活性等位基因的基因型。分别统计3组受检对象基因型分布、各等位基因的频率,和各组的RISP、9-OH-RISP、RISP+9-OH-RISP和9-OH-RISP/RISP。结果第1组有23例,包含WT/WT基因型13例,*2/*2基因型7例,WT/*2基因型3例;第2组有51例,包含WT/*10基因型38例,*2/*10基因型8例,*2/*41基因型1例,WT/*41基因型4例;第3组有46例,包含*10/*10基因型44例,*10/*41基因型2例;未检测到*4等位基因。所有基因型中WT等位基因频率为29.6%,*2等位基因频率为10.8%,*10等位基因频率为56.7%,*41等位基因频率为2.9%。3组受检者的9-OH-RISP/RISP比值:第1组为15.24±5.77,第2组为11.06±4.56,第3组为2.39±1.06,第3组受检者的9-OH-RISP/RISP比值分别与1组和2组比较,差异均有统计学意义(P<0.001)。结论*10等位基因频率在受检对象中频率最高,其与WT等位基因和*2等位基因频率之和在人群中超过95%;携带1个降低CYP2D6酶活性等位基因的个体对利培酮代谢速率的影响较小,而携带2个降低CYP2D6酶活性等位基因的个体,可对利培酮代谢速率产生较显著的影响。Objective To investigate the effect of CYP2D6 gene polymorphism on risperidone (RISP) metabolism in schizophrenic patients. Methods CYP2D6 allele polymorphisms including *10,*4,*41 and *2 was detected by real-time fluorescent PCR in 120 schizophrenic patients who have taken risperidone continually. Alleles without SNP mutations were classified as wild-type (WT). At the same time, serum risperidone and 9-hydroxyrisperidone concentration of all patients were detected by mass spectrometric analysis. Some samples were selected for DNA sequencing of CYP2D6*10, which is the most common CYP2D6 allele in Oriental population. The 120 patients were divided into three groups according to their allele variants. Group 1 was defined as carriers of two functional alleles, group 2 was defined as carriers of one defective allele, group 3 was defined as carriers of two defective alleles. Genotype distributions, alleles frequencies, RISP, 9-oh-RISP, RISP+9-OH-RISP,9-oh-RISP/RISP among three groups were calculated. Results Group 1 amount to 23 cases including 13 cases of WT/WT, 7 cases of *2/*2, 3 cases of WT/*2. Group 2 amount to 51 cases, including 38 cases of WT/*10, 8 cases of *2/*10, 1 case of *2/*41, 4 cases of WT/*41. Group 3 amount to 46 cases, including 44 cases of *10/*10, 2 cases of *10/*41. The *4 allele was not detected. The allele frequency of WT,*2,*10 and *41 was 29.6%, 10.8%, 56.7% and 2.9%, respectively. The 9-hydroxyrisperidone/risperidone-ratio of three groups were 15.24±5.77, 11.06±4.56 and 2.39±1.06, respectively. There was a significant difference in 9-hydroxyrisperidone/risperidone-ratio between Group 3 and the first two groups (P<0.001). Conclusions The frequency of *10 allele was the highest among the subjects. The frequency of WT and *2 allele was over 95% in the population. Individuals carrying one defective allele of CYP2D6 will decrease the rate of risperidone metabolism slightly, while individuals carrying two defective alleles of CYP2D6 may decrease the rate of risperidone metabolism significantly.

关 键 词：精神分裂症 细胞色素P450 CYP2D6 多态现象 遗传 利哌立酮 

分 类 号：R749.3[医药卫生—神经病学与精神病学] R440[医药卫生—临床医学]