Effects of Gene Polymorphisms on Warfarin Trough Concentration and Maintenance Dose

OBJECTIVE To investigate the distribution of VKORC1(-1639G/A), CYP2C9*3, CYP4F2(rs2108622) and CYP2C19*2 gene polymorphism in China population with atrial fibrillation, and then clarify its effect on Trough concentration and maintenance dose of warfarin. METHODS Warfarin blood samples were collected from 75 patients with atrial fibrillation, the trough concentrations were detected by HPLC-UV and genotypes were measured by PCR-RFLP method. The association between different genotypes on concentration and maintenance dose of warfarin were analyzed. RESULTS Warfarin with trough concentrations of 0.5-<1.0 μg·mL^-1, 1.0-2.0 μg·mL^-1 and >2.0 μg·mL^-1 showed higher curative effect(69.23%, 82.6%, 63.41%) than that with 0.5 μg·mL^-1(48.39%) (P<0.05), while between 0.5-<1.0 μg·mL^-1 and >2.0 μg·mL^-1 showed similar curative effect. The allele frequency of VKORC1(-1639G/A), CYP2C9*3, CYP4F2(rs2108622) and CYP2C19*2 were 8.65%, 7.35%, 20%, 30%, respectively. Significant difference of warfain trough concentrations were observed between VKORC1 (-1639G/A) AA and AG/GG as well as CYP4F2(rs2108622) CC and CT/TT genotype(P<0.01), while not among those with CYP2C9*3 and CYP2C19*2 genotypes. Maintenance dose of warfarin in patients with VKORC1(-1639G/A) AG/GG, CYP2C9*3 *1/*1 and CYP4F2(rs2108622) CT/TT were significantly higher than those with VKORC1(-1639G/A) AA, CYP2C9*3 *1/*3 and CYP4F2(rs2108622) CC genotype(P<0.01), respectively. However, there was no statistical significance in those with CYP2C19*2 genotypes. CONCLUSION VKORC1(-1639G/A), CYP2C9*3 and CYP4F2(rs2108622) gene polymorphism significantly affect the maintenance warfarin dose of patients with atrial fibrillation. Furthermore, VKORC1 (-1639G/A) and CYP4F2(rs2108622) gene polymorphism have a close effect on warfarin trough concentration.