CYP1A2基因多态性对精神分裂症患者奥氮平血药浓度的影响

闫盼; 宋明芬; 王晟东; 李静; 王姝琪; 汪程鹏; 刘健; 李欣; 施剑飞

doi:10.16766/j.cnki.issn.1674-4152.001636

CYP1A2基因多态性对精神分裂症患者奥氮平血药浓度的影响

doi: 10.16766/j.cnki.issn.1674-4152.001636

闫盼^1,2,
宋明芬^1,2,
王晟东^1,2,
李静^1,2,
王姝琪^1,2,
汪程鹏^2,3,
刘健^2,3,
李欣^2,3,
施剑飞^2,3, ,

1. 杭州市第七人民医院分子生物学实验室, 浙江杭州 310013;
2. 浙江大学医学院精神卫生中心, 浙江杭州 310013;
3. 杭州市第七人民医院精神科, 浙江杭州 310013

基金项目:

浙江省自然科学青年基金(LQ13H090003)

浙江省医药卫生科技计划项目(2020KY222)

国家自然科学青年基金(81601183)

浙江省科技厅重点研发计划项目(2015C03054)

详细信息

通讯作者:
施剑飞,E-mail:shijf659293@163.com

中图分类号: R749.3;R446
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- 被引次数: 0
出版历程
- 收稿日期: 2019-09-12
- 网络出版日期: 2022-08-06

Effect of CYP1A2 gene polymorphism on plasma concentration of olanzapine in schizophrenic patients

YAN Pan^1,2,
SONG Ming-fen^1,2,
WANG Sheng-dong^1,2,
LI Jing^1,2,
WANG Shu-qi^1,2,
WANG Cheng-peng^2,3,
LIU Jian^2,3,
LI Xin^2,3,
SHI Jian-fei^{2,3
, ,}

Laboralory of Molecular Biology, the Seventh Peoples Hospital of Hangzhou, Hangzhou, Zhejiang 310013, China

摘要

摘要: 目的探讨细胞色素P450 1A2(CYP1A2)基因多态性对精神分裂症患者奥氮平血药浓度的影响,为奥氮平的个体化给药提供参考。方法选取2017年6月—2018年12月期间在杭州市第七人民医院使用奥氮平治疗的226例精神分裂症患者为研究对象,采集血液,应用超高效液相色谱-串联质谱法测定奥氮平血药浓度,采用多重高温连接酶检测反应技术检测CYP1A2*1C和CYP1A2*1F基因多态性,并根据这2个基因多态性位点把CYP1A2基因型分为高活性型(HA)和低活性型(LA),比较不同基因型之间奥氮平血药浓度的差异。结果 GG/AA、GG/CA、GA/AA型患者奥氮平血药浓度明显低于野生GG/CC型[(2.17±0.79)ng/(mL·mg)、(2.53±1.10)ng/(mL·mg)、(2.44±0.79)ng/(mL·mg) vs.(2.99±1.00)ng/(mL·mg),F=3.312,P<0.05];GG/CC、GA/CA、AA/AA型之间以及GG/AA、GG/CA、GA/AA型之间血药浓度差异无统计学意义(P>0.05);HA型血药浓度明显低于LA型[(2.43±0.96)ng/(mL·mg) vs.(2.91±1.06)ng/(mL·mg),t=3.561,P<0.05],并且CYP1A2酶活性与血药浓度呈负相关(r=-0.232,P<0.05)。结论 CYP1A2基因多态性可影响奥氮平血药浓度,GG/AA、GG/CA、GA/AA型患者用奥氮平治疗时血药浓度偏低,临床医生用药时应适当予以关注。
- 精神分裂症 /
- 奥氮平 /
- CYP1A2基因多态性 /
- 血药浓度
Abstract: Objective To investigate the effect of cytochrome P450 1 A2(CYP1 A2) gene polymorphism on plasma concentration of olanzapine in schizophrenic patients, and to provide reference for the individualized administration of olanzapine. Methods A total of 226 schizophrenic patients treated with olanzapine in Hangzhou Seventh People's Hospital from June 2017 to December 2018 were selected as subjects in the study. The plasma concentration of olanzapine was determined by ultra-high-performance liquid chromatography-tandem mass spectrometry. The gene polymorphisms of CYP1 A2*1 C and CYP1 A2*1 F were detected by improved multiple ligase detection reaction, and the CYP1 A2 genotypes were classified into high activity genotype(HA) and low activity genotype(LA) based on these two gene polymorphism sites. Then the difference in plasma concentration of olanzapine among different genotypes were compared. Results The plasma concentrations of olanzapine in the genotypes of GG/AA, GG/CA and GA/AA were obviously lower than that in the wild GG/CC genotype [(2.17±0.79)ng/(mL·mg),(2.53±1.10)ng/(mL·mg),(2.44±0.79)ng/(mL·mg) vs.(2.99±1.00)ng/(mL·mg),F=3.312,P<0.05]. However, there was no significant difference in the genotypes of GG/CC,GA/CA and AA/AA or in the genotypes of GG/AA,GG/CA and GA/AA(P>0.05).The plasma concentration of olanzapine in high activity genotype was obviously lower than that in low activity genotype [(2.43±0.96)ng/(mL·mg) vs.(2.91±1.06)ng/(mL·mg),t=3.561,P<0.05], and the activity of CYP1 A2 was negatively correlated with the plasma concentration of olanzapine(r=-0.232, P<0.05). Conclusion CYP1 A2 gene polymorphism could affect the plasma concentration of olanzapine. The CYP1 A2 genotypes of GG/AA, GG/CA and GA/AA had low plasma concentrations of olanzapine, and clinicians should pay appropriate attention to it when using olanzapine.
- Schizophrenia /
- Olanzapine /
- CYP1A2 gene polymorphism /
- Plasma concentration