Impact of CYP2C19 gene polymorphism on warfarin maintenance doses in patients with non-valvular atrial fibrillation

• First report about CYP2C19*2 and *3 polymorphism and warfarin maintenance dose.
• The patients with CYP2C19*1/*1 had the lowest warfarin maintenance dose.
• CYP2C19*1/*2 and *1/*3 had lower warfarin dose than CYP2C19*2/*2 and *2/*3.
• Warfarin maintenance dose: extensive < intermediate < poor metabolizer.
• CYP2C19 genotype may be used as an indicator for medication in NVAF patients.

BackgroundPharmacogenetics 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.MethodsIn 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.ResultsCYP2C19 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).ConclusionCYP2C19 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.