VKORC1 genotypes are associated with response to warfarin but free warfarin concentration during initial anticoagulation in healthy Chinese volunteers  

作　　者：XIE Shuang LIU Hong TIAN Lei JIANG Juan-juan CHEN Guo-liang LIU Li-wei XU Li LI Yi-shi 

机构地区：[1]Key Laboratory of Clinical Trial Research in Cardiovascular Drugs, Ministry of Health, Fu Wai Hospital , Chinese Academy of Medical Sciences, Beijing 100037, China [2]Peking Union Medical College , Chinese Academy of Medical Sciences, Beijing 100037, China

出　　处：《Chinese Medical Journal》2009年第18期2117-2122,共6页中华医学杂志（英文版）

摘　　要：Background The genetic variations in VKORC1 modulate the stable responses to warfarin administration. But the role of VKORC1 polymorphisms during the initial anticoagulation and elimination period in the Hart Chinese population is not clear. Methods Twenty-four healthy Chinese volunteers were grouped according to their VKORC1 genotype. Twelve subjects were in the 3 mg group and 12 in the 6 mg group. VKORC1 genotypes were determined by a polymerase chain reaction （PCR） based restriction fragment length polymorphism （RFLP） assay and sequencing. The international normalized ratio （INR） was measured with an ACL9000 coagulation analyser. Plasma free warfarin concentration was measured with LC/MS/MS. Results In the initial anticoagulation period, the -1639AG and 1173TC carriers compared with the -1639AA and 1173TT carriers had a low INR value. The differences between genotypes with regard to INR values were more obvious in the 3 mg subjects （P 〈0.05）, and were not significantly different among the 6 mg subjects （P〉0.05）. On the contrary, no significant difference of plasma free warfarin concentration between genotypes was observed in each dosage group. It took 96 hours for the INR value and 144 hours for the free warfarin plasma concentration to come back to baselines after the last dose. No significant difference among genotypes and dosing groups was detected in the elimination phase （P〉0.05）. Conclusion VKORC1 polymorphisms are associated with differences in the initial response to warfarin when given at fixed doses, without affecting, as expected, its plasma concentration.Background The genetic variations in VKORC1 modulate the stable responses to warfarin administration. But the role of VKORC1 polymorphisms during the initial anticoagulation and elimination period in the Hart Chinese population is not clear. Methods Twenty-four healthy Chinese volunteers were grouped according to their VKORC1 genotype. Twelve subjects were in the 3 mg group and 12 in the 6 mg group. VKORC1 genotypes were determined by a polymerase chain reaction （PCR） based restriction fragment length polymorphism （RFLP） assay and sequencing. The international normalized ratio （INR） was measured with an ACL9000 coagulation analyser. Plasma free warfarin concentration was measured with LC/MS/MS. Results In the initial anticoagulation period, the -1639AG and 1173TC carriers compared with the -1639AA and 1173TT carriers had a low INR value. The differences between genotypes with regard to INR values were more obvious in the 3 mg subjects （P 〈0.05）, and were not significantly different among the 6 mg subjects （P〉0.05）. On the contrary, no significant difference of plasma free warfarin concentration between genotypes was observed in each dosage group. It took 96 hours for the INR value and 144 hours for the free warfarin plasma concentration to come back to baselines after the last dose. No significant difference among genotypes and dosing groups was detected in the elimination phase （P〉0.05）. Conclusion VKORC1 polymorphisms are associated with differences in the initial response to warfarin when given at fixed doses, without affecting, as expected, its plasma concentration.

关 键 词：WARFARIN VKORC1 genotype international normalized ratio free warfarin plasma concentration 

分 类 号：R686[医药卫生—骨科学]