Hongshen Zhang1, Kezhong Ma1, Wenwei Liu1, Feng Yang1, Jianfei Liu1, Hanyun Zhou2. 1. Department of Cardiology, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science, Xiangyang, 441021, PR China. 2. Department of Cardiology, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science, Xiangyang, 441021, PR China. Electronic address: Zhou_xyzxyy@126.com.
Abstract
BACKGROUND: Pharmacogenetics has provided compelling evidence towards the influence of gene polymorphisms on warfarin therapies. This study aimed to determine the impact of CYP2C19 gene polymorphism on warfarin maintenance doses in patients with non-valvular atrial fibrillation for the progress in overcoming obstacles facing warfarin pharmacogenetics. METHODS: In this study, we utilized polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) to investigate the distribution of CYP2C19*2 and *3 gene polymorphism in patients with NVAF. In order to exclude the interference of basic indexes, we compared the association between different genotypes and warfarin maintenance doses. And the comparisons among extensive metabolizer, intermediate metabolizer and poor metabolizer were performed. RESULTS: CYP2C19 mutation accounted for 88.07% of in total NVAF patients, which was 7.38 times of CYP2C19*1/*1 (11.93%). No significant association was observed between different genotypes and basic indexes. The warfarin maintenance dose of patients with CYP2C19*1/*1 was significantly higher than those with other five genotypes (all P<0.05). Besides, the warfarin maintenance doses of patients with CYP2C19*1/*2 and *1/*3 were remarkably higher than those with *2/*2 and *2/*3 (P<0.05). The warfarin maintenance doses of patients with extensive metabolizer were dramatically higher than those with intermediate metabolizer and poor metabolizer (both P<0.05), and also the patients with intermediate metabolizer had higher warfarin maintenance doses than those with poor metabolizer (P<0.05). CONCLUSION: CYP2C19 gene polymorphism can affect maintenance dose of warfarin, with the amount of warfarin dose ranked among different genotypes as follow: CYP2C19*2/*2, CYP2C19*2/*3 and CYP2C19*3/*3<CYP2C19*1/*2 and CYP2C19*1*<CYP2C19*1/*1.
BACKGROUND: Pharmacogenetics has provided compelling evidence towards the influence of gene polymorphisms on warfarin therapies. This study aimed to determine the impact of CYP2C19 gene polymorphism on warfarin maintenance doses in patients with non-valvular atrial fibrillation for the progress in overcoming obstacles facing warfarin pharmacogenetics. METHODS: In this study, we utilized polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) to investigate the distribution of CYP2C19*2 and *3 gene polymorphism in patients with NVAF. In order to exclude the interference of basic indexes, we compared the association between different genotypes and warfarin maintenance doses. And the comparisons among extensive metabolizer, intermediate metabolizer and poor metabolizer were performed. RESULTS:CYP2C19 mutation accounted for 88.07% of in total NVAF patients, which was 7.38 times of CYP2C19*1/*1 (11.93%). No significant association was observed between different genotypes and basic indexes. The warfarin maintenance dose of patients with CYP2C19*1/*1 was significantly higher than those with other five genotypes (all P<0.05). Besides, the warfarin maintenance doses of patients with CYP2C19*1/*2 and *1/*3 were remarkably higher than those with *2/*2 and *2/*3 (P<0.05). The warfarin maintenance doses of patients with extensive metabolizer were dramatically higher than those with intermediate metabolizer and poor metabolizer (both P<0.05), and also the patients with intermediate metabolizer had higher warfarin maintenance doses than those with poor metabolizer (P<0.05). CONCLUSION:CYP2C19 gene polymorphism can affect maintenance dose of warfarin, with the amount of warfarin dose ranked among different genotypes as follow: CYP2C19*2/*2, CYP2C19*2/*3 and CYP2C19*3/*3<CYP2C19*1/*2 and CYP2C19*1*<CYP2C19*1/*1.