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Impact of CYP2C9*3, VKORC1-1639, CYP4F2rs2108622 genetic polymorphism and clinical factors on warfarin maintenance dose in Han-Chinese patients
Liang, Ruijuan; Li, Lei; Li, Cuilan; Gao, Yuanfeng; Liu, Wenling; Hu, Dayi; Sun, Yihong
关键词Warfarin Pharmacogenomics CYP4F2 CYP2C9 VKORC1
刊名JOURNAL OF THROMBOSIS AND THROMBOLYSIS
2012-07-01
DOI10.1007/s11239-012-0725-7
34期:1页:120-125
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Hematology ; Peripheral Vascular Disease
研究领域[WOS]Hematology ; Cardiovascular System & Cardiology
关键词[WOS]REDUCTASE COMPLEX SUBUNIT-1 ; AFRICAN-AMERICANS ; INTERINDIVIDUAL VARIABILITY ; JAPANESE PATIENTS ; CYP4F2 RS2108622 ; CYP2C9 ; REQUIREMENTS ; ASSOCIATION ; POPULATION ; GENOTYPES
英文摘要

To evaluate the impact of gene polymorphisms of Cytochrome P450 2C9 (CYP2C9), Vitamin K epoxide reductase complex subunit 1 (VKORC1) and Cytochrome P450 4F2 (CYP4F2) and clinical factors on warfarin maintenance dose in Han-Chinese patients from main land. DNA was extracted from 115 patients taking warfarin for more than 3 months with a stable international normalized ratio (INR) and genotyped for CYP2C9*3, VKORC1-1639 and CYP4F2 (rs2108622) polymorphisms using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Univariate analysis and multiple regression analysis were undertaken to assess the effect of genetic and clinical factors on the warfarin maintenance dose. Our study demonstrated that patients carrying CYP4F2 CT or TT allele needed a significantly higher warfarin dose compared to those carrying CC ((3.36 +/- A 0.14 mg/d vs. 2.77 +/- A 0.14 mg/d), P = 0.004). We also confirmed CYP2C9 *3 variant was related to lower warfarin dose (2.01 +/- A 0.23 mg/d) requirement compared to wild type (3.21 +/- A 0.11 mg/d) (P = 0.001). VKORC1-1639 AG genotype was associated with a higher maintenance dose compared to those with the AA genotype (4.06 +/- A 0.21 mg/d vs. 2.95 +/- A 0.11 mg/d, P < 0.001). The multiple linear regression model including VKORC1-1639G > A, CYP2C9, CYP4F2 and clinical factors (body surface area (BSA) and age) could explain 42 % of the variance in the warfarin maintenance dose. We developed a dose algorithm based on genetic polymorphism and clinical variables for Han-Chinese patients and evaluated its performance. CYP4F2 rs2108622 has a small but significant association with warfarin stable dose in Han-Chinese population.

语种英语
WOS记录号WOS:000305523300017
引用统计
被引频次:35[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/63896
专题北京大学第二临床医学院
北京大学医学部管理机构_医学部
北京大学第二临床医学院_老年科
北京大学第二临床医学院_心血管内科
作者单位Peking Univ, Peoples Hosp, Ctr Heart, Beijing 100044, Peoples R China
推荐引用方式
GB/T 7714
Liang, Ruijuan,Li, Lei,Li, Cuilan,et al. Impact of CYP2C9*3, VKORC1-1639, CYP4F2rs2108622 genetic polymorphism and clinical factors on warfarin maintenance dose in Han-Chinese patients[J]. JOURNAL OF THROMBOSIS AND THROMBOLYSIS,2012,34(1):120-125.
APA Liang, Ruijuan.,Li, Lei.,Li, Cuilan.,Gao, Yuanfeng.,Liu, Wenling.,...&Sun, Yihong.(2012).Impact of CYP2C9*3, VKORC1-1639, CYP4F2rs2108622 genetic polymorphism and clinical factors on warfarin maintenance dose in Han-Chinese patients.JOURNAL OF THROMBOSIS AND THROMBOLYSIS,34(1),120-125.
MLA Liang, Ruijuan,et al."Impact of CYP2C9*3, VKORC1-1639, CYP4F2rs2108622 genetic polymorphism and clinical factors on warfarin maintenance dose in Han-Chinese patients".JOURNAL OF THROMBOSIS AND THROMBOLYSIS 34.1(2012):120-125.
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