Abstract
BackgroundIndividuals with implanted mechanical valve prostheses require lifelong anticoagulation therapy with warfarin. The narrow therapeutic index of warfarin makes it difficult to dose and maintain proper anticoagulation. A number of single nucleotide polymorphisms (SNPs) affecting vitamin K or warfarin metabolism have been shown to affect warfarin dosing. Our aim was to study the effect of the CYP4F2 rs2108622-1347 (C > T) variant on warfarin dosing in Chinese patients.MethodsWe studied 352 patients after heart valve replacement surgery. Warfarin dosing for patients was adjusted to achieve 1.8 ≤ INR ≤ 2.5. We determined the presence of SNPs in CYP4F2 in these patients and investigated their association with warfarin dosing.ResultsWe found the frequency of the CYP4F2 rs2108622 C allele was 79.5% and T-allele frequency was 20.5%. The warfarin dose requirement for CC individuals was significantly lower than that for CT or TT individuals (P < 0.05). TT-homozygous individuals required a 0.56 mg/day higher dose of warfarin than their CC counterparts.ConclusionsThis study demonstrates that CYP4F2 rs2108622 significantly affects the warfarin dose requirement to achieve adequate anticoagulant activity in Chinese individuals. Genotyping of this SNP may allow clinicians to determine the initiation dose for patients following valve-replacement surgery in China.
Highlights
Individuals with implanted mechanical valve prostheses require lifelong anticoagulation therapy with warfarin
Patients started by taking 2.5 mg/day warfarin after the prosthetic valve implantation and the international normalization ratio (INR) measured at the 8th day
Patients that reached 1.8 ≤ INR ≤ 2.5 were tested for INR weekly for four months, monthly for three months when maintained in 1.8 ≤ INR ≤ 2.5
Summary
Individuals with implanted mechanical valve prostheses require lifelong anticoagulation therapy with warfarin. Patients with implanted mechanical valve prosthesis are committed to lifelong anticoagulation therapy with warfarin [1]. Recent studies have analyzed genetic variations in patients taking warfarin and identified several single nucleotide polymorphisms (SNPs) that affect warfarin dosing. Two SNPs have been shown by many investigators to affect warfarin dosage, one in the vitamin K 2,3epoxide reductase complex: VKORC1-1639 G > A, and the other involving the liver cytochrome P450 2C9 isozyme: CYP2C9 rs1057910 [6,7,8,9]. A SNP in another P450 isozyme, CYP4F2 rs2108622-1347 C > T, has been shown to be responsible for differences in warfarin dosage for many individuals [10,11,12]. Different investigators have arrived at different conclusions regarding the impact of this SNP [10,12,13,14,15], and it remains a hot spot in warfarin-therapy research
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