Effect of gene polymorphims on the warfarin treatment at initial stage

Abstract

The adverse reactions of warfarin that were found mainly occurred in the first month. This study was carried out to observe the effect of gene polymorphisms on the warfarin therapy at the initial stage. Four-hundred and sixty Chinese patients began warfarin treatment with daily 2.5 mg after heart valve replacement operations were enrolled. The daily international normalized ratio (INR) for anticoagulation were recorded till the seventh day. Blood samples were collected and used to detect genotypes for VKORC1 rs7294, CYP2C9 rs1057910, CYP4F2 rs2108622 and ORM1 rs17650. INR and their changes were compared among genotypes. INR was partially correlated with the VKORC1 rs7294, CYP2C9 rs1057910, CYP4F2 rs2108622 and ORM1 rs17650 polymorphisms from the third, fourth and sixth day on, respectively. VKORC1 rs7294 and CYP4F2 rs2108622 carriers responded lower than the wild genotype, whereas CYP2C9 rs1057910 and ORM1 rs17650 carriers responded higher, respectively. Fifty percent of AA/*1*3/CC/*S*S patients and 16% of AA/*1*1/CC/*S*S patients were over anticoagulation treated with INR >4.0 at the third day. Ninety percent of VKORC1 rs7294 carrier patients have INR <1.63, a mark of the 25% of lower responders of the wild genotype. Our study provided another kind of evidence that VKORC1 rs7294, CYP2C9 rs1057910, CYP4F2 rs2108622 and ORM1 rs17650 affected the action of warfarin in different styles. Patients with AA/*1*1/CC/*S*S, AA/*1*3/CC/*S*S should use a less initial dosage to avoid over anticoagulation, and patients with VKORC1 rs7294 should use larger initial dose to proof an effective therapy.

Genetic polymorphism of CYP2C9 and VKORC1 in the Nigerian population: significance for warfarin therapy in the population

“…This variant has been reported to impact significantly on warfarin efficacy, especially at the early stages of therapy commencement, in a study of 460 Chinese patients. 17 The same study observed suboptimal INR values in about 90% of patients who were carriers of VKORC1*3 after 7 days of daily 2.5 mg warfarin administration. Another study in Sudanese subjects who had been on warfarin for at least three months showed that the mean daily dose was about 14% higher in homozygous and heterozygous VKORC1*3 carriers, 18 while variability in warfarin plasma levels and an expected adjustment of warfarin doses was also explainable by VKORC1*3 in addition to CYP2C9*8 in South Africans.…”

The timing of symptomatic pulmonary embolism in patients with non-warfarin following elective primary total joint arthroplasty

“…Therefore, the anticoagulation-effect of warfarin is somewhat delayed. Hence, patients with warfarin often have complications such as thrombosis and hemorrhage in the early stage [15][16][17]. In contrast, low molecular weight heparin or rivaroxaban usually reach peaks of blood concentration at 2-4 hours after administration [18][19][20], which may be one of the important reasons for the late onset of symptomatic PE in our research.…”

A Novel Polymorphism in the Promoter of theCYP4A11Gene Is Associated with Susceptibility to Coronary Artery Disease

“…20-HETEs possess multifaceted effects on cardiovascular functions including those implicated to the pathogenesis of CVD: stimulation of smooth muscle contractility, migration, and proliferation, as well as activation of endothelial cell dysfunction, angiogenesis, and inflammation [ 9 , 15 ]. Cytochrome P450 4A11 and 4F2 are the major 20-HETE-producing CYP4 isoforms in humans [ 16 , 17 ] which also participate in the metabolism of several drugs including those used for therapy of CVDs [ 18 ].…”