Effects of CYP2C9 and VKORC1 Genetic Polymorphisms on Maintenance Dosage and Anticoagulation Effect of Warfarin in Patients after Undergoing Mechanical Heart Valve Prostheses Replacement

OBJECTIVE:To evaluate the effects of CYP2C9 and VKORC1 gene polymorphisms on maintenance dosage and its anticoagulant effect of warfarin in order to provide evidence for establishing individualized dosage model for patients after undergoing heart mechanical valve replacement. METHODS: Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP)method was applied to detect CYP2C9 and VKORC1 receptor gene polymorphisms in 119 patients from Fuzhou after undergoing heart mechanical valve replacement. The indexes such as gender,age,body weight,warfarin maintenance dosage, the time to achieve stable anticoagulation,incidences of over-anticoagulant and adverse reactions were recorded. RESULTS: CYP2C93 and CYP2C9-65G/C genotypes were correlated with low warfarin maintenance dosage but VKORC1-1639A/G geno-type was correlated with high warfarin maintenance dosage. The CYP2C9 heterozygote carriers had an increased risk of over-anticoagulation yet whose risk of bleeding events did not increased. The time to achieve stable anticoagulation was longer in patients who carry CYP2C9 and VKORC1 mutation alleles. CONCLUSIONS:Detection of CYP2C9 and VKORC1 genotypes prior to medication and predicating warfarin dosage may result in lower incidence of over-anticoagulation and reduce the dosage-adjusting time of warfarin.