Abstract:

Objective To investigate the effects of CYP2C9*3 and VKORC1-1639G>A single nucleotide polymorphisms on warfarin (WFR) in prevention of deep venous thrombosis (DVT) of lower limbs after orthopedic surgery. Methods Two hundred and fourteen patients treated with WRN in prevention of DVT of lower limbs after orthopedic surgery were selected, the CYP2C9*3 and VKORC1-1639G>A polymorphisms were screened by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis, and the correlation of distribution of gene polymorphism with outcome of preventive treatment by WRN was statistically analysed. Results In these 214 patients, the frequencies of CYP2C9*3 alleles were 94.9% and 5.1% respectively, and the frequencies of VKORC1-1639G>A mutation in G and A alleles were 10.5% and 89.5% respectively. The distributions of *1/*1, *1/*3 and *3/*3 genotypes in CYP2C9*3 gene were 90.7%, 8.4% and 0.9% respectively, and the distributions of GG, GA and AA genotypes in VKORC1-1639G> A were 0.9%, 19.2% and 79.9% respectively. Both frequency distributions were in line with the Hardy-Weinberg equilibrium. Individual stable doses of WRN after operation were grouped based on the distributions of gene polymorphisms, and it was found that the stable doses of WRN were correlated with the gene polymorphisms of VKORC1-1639G>A and CYP2C9*3 (P<0.01). Besides, the incidences of DVT after WRN treatment varied among patients with different genotypes. Conclusion VKORC1-1639G>A and CYP2C9*3 polymorphisms may lead to the changes of stable doses of WRN in prevention of DVT of lower limbs after orthopedic surgery, and may be correlated to the clinical efficacy of WRN.

Key words: gene polymorphism, CYP2C9, VKORC1, orthopedic surgery, thrombosis, vein