p450 - publications

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1. J Thromb Thrombolysis. 2012 Apr 22. [Epub ahead of print]

Impact of CYP2C9*3, VKORC1-1639, CYP4F2rs2108622 genetic polymorphism and
clinical factors on warfarin maintenance dose in Han-Chinese patients.

Liang R, Li L, Li C, Gao Y, Liu W, Hu D, Sun Y.

Heart Center, Peking University People's Hospital, #11 Xizhimen South Street,
Xichengqu, Beijing, 100044, China.

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 ± 0.14 mg/d vs. 2.77 ± 0.14 mg/d), P = 0.004). We also confirmed CYP2C9 *3
variant was related to lower warfarin dose (2.01 ± 0.23 mg/d) requirement
compared to wild type (3.21 ± 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 ± 0.21 mg/d vs. 2.95 ± 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.

PMID: 22528326 [PubMed - as supplied by publisher]