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学科主题: 临床医学
题名:
Impact of CYP2C9*3, VKORC1-1639, CYP4F2rs2108622 genetic polymorphism and clinical factors on warfarin maintenance dose in Han-Chinese patients
作者: 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
发表日期: 2012-07-01
DOI: 10.1007/s11239-012-0725-7
卷: 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
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/63896
Appears in Collections:北京大学第二临床医学院_期刊论文

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作者单位: Peking Univ, Peoples Hosp, Ctr Heart, Beijing 100044, Peoples R China

Recommended Citation:
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.
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