IR@PKUHSC  > 北京大学基础医学院  > 药理学系
学科主题基础医学
Influence of CYP3A5 and MDR1 Genetic Polymorphisms on Urinary 6 beta-Hydroxycortisol/Cortisol Ratio After Grapefruit Juice Intake in Healthy Chinese
Li, Dan1; Abudula, Aziguli2; Abulahake, Muhutar3; Zhu, An-Ping4; Lou, Ya-Qing1; Zhang, Guo-Liang1
关键词Genetic Polymorphism Cyp3a Activity Mdr1 Grapefruit Juice Chinese
刊名JOURNAL OF CLINICAL PHARMACOLOGY
2010-07-01
DOI10.1177/0091270009354997
50期:7页:775-784
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Pharmacology & Pharmacy
资助者National Natural Science Foundation of China ; Beijing University Center for Human Disease Genomics ; National Natural Science Foundation of China ; Beijing University Center for Human Disease Genomics
研究领域[WOS]Pharmacology & Pharmacy
关键词[WOS]FREE CORTISOL ; CYTOCHROME-P450 ; INHIBITION ; 3A4 ; PHARMACOKINETICS ; VARIABILITY ; POPULATIONS ; INDUCTION ; BASAL ; METABOLISM
英文摘要

Interindividual variability of cytochrome P450 (CYP) 3A inhibition by grapefruit juice was investigated in relation to CYP3A5 and multidrug resistance gene (MDR) 1 genetic polymorphisms in Chinese Han, Uygur, and Kazakh healthy subjects. The measurement of urinary 6 beta-hydroxycortisol/cortisol ratio was used to evaluate CYP3A activity in vivo by high-performance liquid chromatography. CYP3A5*3 and MDR1 C1236T, G2677T/A, and C3435T polymorphisms were analyzed by polymerase chain reaction restriction fragment length polymorphism. After grapefruit juice intake, urinary ratios significantly decreased in 3 Chinese ethnic groups (P<.001). Kazakh had a larger decrease of urinary ratio compared to that of Han (P<.05), and the latter had similar decrease with Uygur. Furthermore, Chinese healthy subjects carrying CYP3A5*3/*3 and MDR1(1236-2677-3435) T-T-T/T-T-T genotypes were found to have the largest reduction of urinary ratio (mean, 61.4%; 95% confidence interval, 53.4%-69.5%), whereas *1/*3 subjects carrying MDR1(1236-2677-3435) C-G-C/C-G-C genotypes had the lowest reduction (mean, 25.9%; 95% confidence interval, 3.1%-48.8%; P<.01). In conclusion, both CYP3A5*3 and MDR1 variants influenced the extent of CYP3A inhibition by grapefruit juice in Chinese healthy subjects. The genetic variations influencing the CYP3A inhibitive phenotype might be helpful to explain the individual variability of grapefruit juice-drug interactions.

语种英语
所属项目编号30171097 ; 30371665 ; 2000A-1
资助者National Natural Science Foundation of China ; Beijing University Center for Human Disease Genomics ; National Natural Science Foundation of China ; Beijing University Center for Human Disease Genomics
WOS记录号WOS:000278829600005
Citation statistics
Cited Times:14[WOS]   [WOS Record]     [Related Records in WOS]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/55581
Collection北京大学基础医学院_药理学系
作者单位1.Beijing Univ, Basic Med Sch, Dept Pharmacol, Beijing 100871, Peoples R China
2.Cent Univ Nationalities, Dept Uygur Language & Literature, Beijing, Peoples R China
3.Cent Univ Nationalities, Dept Kazakh Language & Literature, Beijing, Peoples R China
4.Cent Univ Nationalities, Affiliated Hosp, Beijing, Peoples R China
Recommended Citation
GB/T 7714
Li, Dan,Abudula, Aziguli,Abulahake, Muhutar,et al. Influence of CYP3A5 and MDR1 Genetic Polymorphisms on Urinary 6 beta-Hydroxycortisol/Cortisol Ratio After Grapefruit Juice Intake in Healthy Chinese[J]. JOURNAL OF CLINICAL PHARMACOLOGY,2010,50(7):775-784.
APA Li, Dan,Abudula, Aziguli,Abulahake, Muhutar,Zhu, An-Ping,Lou, Ya-Qing,&Zhang, Guo-Liang.(2010).Influence of CYP3A5 and MDR1 Genetic Polymorphisms on Urinary 6 beta-Hydroxycortisol/Cortisol Ratio After Grapefruit Juice Intake in Healthy Chinese.JOURNAL OF CLINICAL PHARMACOLOGY,50(7),775-784.
MLA Li, Dan,et al."Influence of CYP3A5 and MDR1 Genetic Polymorphisms on Urinary 6 beta-Hydroxycortisol/Cortisol Ratio After Grapefruit Juice Intake in Healthy Chinese".JOURNAL OF CLINICAL PHARMACOLOGY 50.7(2010):775-784.
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