例心衰患者的MDR1和CYP3A基因多态性与地高辛血药浓度的相关性研究

中国临床药理学与治疗学 ›› 2014, Vol. 19 ›› Issue (3): 291-296.

例心衰患者的MDR1和CYP3A基因多态性与地高辛血药浓度的相关性研究

欧阳苍鸿¹, 谢娟²

¹遵义市第一人民医院药剂科,遵义 563000,贵州;
²贵州省人民医院药剂科,贵阳 550002,贵州

收稿日期:2013-04-16 修回日期:2014-02-24 出版日期:2014-03-26 发布日期:2014-04-10
通讯作者: 谢娟,女,主任药师,硕士研究生导师,研究方向:遗传药理学。Tel: 13984090089 E-mail: xiejuan945@sohu.com111
作者简介:欧阳苍鸿,男,硕士,药师,主要研究方向:临床药学。Tel: 18286249990 E-mail: oych_duo@126.com
基金资助:
贵州省自然科学基金“贵州地区肾病患者CYP2D6的遗传变异与药物不良反应分析”(黔科合J字[2006]2068号)

Study on the relationship between the MDR1 and CYP3A genetic polymorphisms and serum digoxin concentration in 111 patients with chronic heart failure

OUYANG Cang-hong¹, XIE Juan²

¹The First People's Hospital of Zunyi, Zunyi 563000, Guizhou, China;
²Guizhou Provincial People's Hospital,Guiyang 550002,Guizhou, China

Received:2013-04-16 Revised:2014-02-24 Online:2014-03-26 Published:2014-04-10

摘要/Abstract

摘要： 目的: 观察中国贵州地区汉族心衰患者中MDR1C3435T、CYP3A4^*18B和CYP3A5^*3等位基因多态性对地高辛血药浓度的影响。方法: 收集111名中国贵州地区汉族心衰患者的血样与地高辛治疗药物浓度监测(TDM)数据,通过PCR-RFLP法分析患者的MDR1C3435T、CYP3A4^*18B及CYP3A5^*3基因型,分析每个基因的多态性对地高辛血药浓度的影响。结果: 70岁以上患者MDR1各基因型组中,野生纯合子(CC)组、突变杂合子(CT)组、突变纯合子(TT)组的地高辛血药浓度依次增高。CC组和CT组较TT组的地高辛血药浓度差异有统计学意义 (P<0.05); CYP3A4和CYP3A5各基因型组之间的地高辛血药浓度差异均无统计学意义 (P>0.05)。结论: MDR1C3435T等位基因突变可使地高辛血药浓度提高;而CYP3A4^*18B和CYP3A5^*3等位基因突变对地高辛的血药浓度无明显影响。

关键词: 基因多态性, MDR1, CYP3A4, CYP3A5, 地高辛

Abstract: AIM: To investigate the impact of MDR1C3435T, CYP3A4^*18B and CYP3A5^*3 genetic polymorphism on serum digoxin concentration in Chinese Han patients with chronic heart failure.METHODS: Drug concentration data of digoxin for a group of 111 unrelated Chinese Han patients with chronic heart failure were retrospectively collected after them taken therapeutic drug monitoring (TDM) of digoxin. And their genotypes of MDR1C3435T, CYP3A4^*18B and CYP3A5^*3 alleles were determined by PCR-RFLP method. We investigated the effect of MDR1C3435T, CYP3A4^*18B and CYP3A5^*3 genetic polymorphism on serum digoxin concentration.RESULTS: In old people (older than 70 years), the serum digoxin concentration in MDR1CC3435 and MDR1TT3435 vs. MDR1TT3435 groups showed a significant difference (P<0.05); But there was no statistical difference on the serum digoxin concentration with CYP3A4^*18B or CYP3A5^*3 genetic polymorphism (P>0.05).CONCLUSION: The effect of MDR1C3435T genetic polymorphism increased the serum digoxin concentration; CYP3A4^*18B or CYP3A5^*3 genetic polymorphism may have no significant effect on the serum digoxin concentration.

Key words: genetic polymorphism, digoxin, MDR1, CYP3A4, CYP3A5

中图分类号:

R968

欧阳苍鸿, 谢娟. 例心衰患者的MDR1和CYP3A基因多态性与地高辛血药浓度的相关性研究[J]. 中国临床药理学与治疗学, 2014, 19(3): 291-296.

OUYANG Cang-hong, XIE Juan. Study on the relationship between the MDR1 and CYP3A genetic polymorphisms and serum digoxin concentration in 111 patients with chronic heart failure[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2014, 19(3): 291-296.

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