韩璐璐
中国医学科学院阜外医院 病理科
OBJECTIVES:To establish an algorithm to predict the warfarin maintenance dose in Chinese Han population and validate the accuracy of this algorithm.METHODS:A total of 488 Chinese Han patients, hospitalized in Fuwai hospital and had a stable dose of warfarin and a target international normalized ratio (INR) of 1.5 to 3.0, were recruited. Indications for warfarin use included prosthetic heart valve, atrial fibrillation and pulmonary embolism. These patients were divided into derivation group (n = 323) and validation group (n = 165) according to the enrollment time. A warfarin maintenance dose algorithm was established based on genetic information, demographic characteristics and concomitant medications by multiple linear regression analysis in derivation group. In the validation group, we evaluated the accuracy of our algorithm by comparing the predicted dose with the actual dose.RESULTS:Our algorithm included VKORC1-1639G > A, CYP2C9*3 and CYP4F2 genotype, age, Body hight, body weight, amiodarone and digoxin use (R(2) = 0.652, P < 0.001) .In the validation group, the average predicted dose by our algorithm had no statistical difference with the actual dose [(3.51 ± 1.03) mg vs. (3.53 ± 1.41) mg, P = 0.779]. Our algorithm identified 100 out of 165 (60.6%) patients in the validation group, whose predicted dose of warfarin was within 20% of the actual dose, and predicted warfarin dose was underestimated in 17.6% (29/165) patients and overestimated in 21.8% (36/165) patients.CONCLUSION:Our algorithm based on VKORC1, CYP2C9 and CYP4F2 polymorphisms can help to predict the warfarin maintenance dose in Chinese Han Population.
Zhonghua xin xue guan bing za zhi 2014
OBJECTIVE:To evaluate the effect of VKORC1, CYP2C9, GGCX, PROC, EPHX1 and CYP4F2 gene polymorphisms on Warfarin maintenance dose variation in Chinese Han Population.METHODS:Four hundred eighty-eight patients with prosthetic heart valves, atrial fibrillation or pulmonary thromboembolism and achieved stable Warfarin dose were enrolled. TaqMan probe or direct sequencing were used to genotype Y9VKORC1, CYP2C9, GGCX, EPHX1 and CYP4F2 gene polymorphisms. Demographic characteristics, stable therapeutic dose of Warfarin and concomitant medications were collected for all patients. The effect of VKORC1, CYP2C9, GGCX, PROC, EPHX1 and CYP4F2 gene polymorphisms, demographic characteristics and concomitant medications on Warfarin daily maintenance dose were analyzed with statistical method.RESULTS:VKORC1 and CYP2C9 gene polymorphisms could explain more than 50% Warfarin maintenance dose variation in recruited patients, while CYP4F2 gene polymorphisms could only explain 1%. GGCX, PROC and EPHX1 gene polymorphisms had no impact no Warfarin maintenance dose. VKORC1 and CYP2C9 gene polymorphisms have a greater impact on Warfarin maintenance dose compared with demographic characteristics and concomitant medications.CONCLUSION:VKORC1 and CYP2C9 gene polymorphisms have a significant impact on Warfarin maintenance dose in Chinese Han population.
Zhonghua yi xue yi chuan xue za zhi = Zhonghua yixue yichuanxue zazhi = Chinese journal of medical genetics 2014
BACKGROUND:Whether two clopidogrel pretreatment strategies prior to elective percutaneous coronary intervention (PCI): a 300 mg loading dose (LD) in clopidogrel naїve patients and a 75 mg maintenance dose (MD) once daily in patients on chronic clopidogrel therapy play the same role in the platelet inhibition in Chinese with different CYP2C19 genotypes remains unknown. We aim to evaluate the impact on platelet inhibition by clopidogrel pretreatment strategy and its interaction effect with CYP2C19 genotype.METHODS:Chinese patients undergoing PCI (n = 840) were assigned to 2×2 groups in the trial according to different clopidogrel pretreatment strategies (470 patients in LD, 370 patients in MD) and CYP2C19 genotypes (494 carriers of any CYP2C19 *2 or *3 loss-of-function allele, 346 non-carriers). The primary outcome was platelet aggregation (PA) as measured by the 10 µmol/L adenosine diphosphate induced light transmission aggregation.RESULTS:Compared with MD group, LD strategy showed a significantly higher PA-((59.22 ± 11.67)% vs. (52.83 ± 12.17)%, P < 0.01), similar PA difference was observed in CYP2C19 loss-of-function carriers compared with non-carriers ((59.41 ± 10.91)% vs. (52.10 ± 12.90)%, P < 0.01). LD patients in either the CYP2C19 loss-of-function allele carrier or non-carrier group showed a significantly higher PA compared with MD group ((61.50 ± 10.61)% vs. (56.84 ± 10.74)%, P < 0.01; (56.06 ± 12.34)% vs. (46.88 ± 11.78)%, P < 0.01, respectively). A quantitative interaction effect was observed between clopidogrel pretreatment strategy and CYP2C19 genotype (P = 0.001).CONCLUSION:The 300 mg LD strategy results in a decreased effect on platelet inhibition compared with the 75 mg MD in Chinese patients receiving clopidogrel prior to PCI, especially in the CYP2C19 2 or 3 loss-of-function allele non-carriers. (ClinicalTrials.gov number NCT01710436)
Chinese medical journal 2014
