Effect of gene polymorphism on warfarin dosage in Chinese Han patients with nonvalvular atrial fibrillation / 中华全科医师杂志

ABSTRACT

Objectives:To investigate the relationships between CYP2C9 and VKORC1 polymorphism and the steady-state dose of warfarin in Chinese Han patients with nonvalvular atrial fibrillation.Methods:A total 544 Chinese Han patients with atrial fibrillation who received warfarin anticoagulant therapy in Department of Cardiology of Beijing Hospital, Tongren Hospital, Xuanwu Hospital, Anzhen Hospital and Tiantan Hospital were enrolled from January 2016 to may 2019. The genotype and allele frequency in exon 1, 2, 3, 7 of CYP2C9 gene and 1639 site of VKORC1 gene were analyzed; and the general information, warfarin steady-state dose and concomitant medication of patients were recorded.Results:There were four genotypes CYP2C9CYP2C9*1*1 (93.57%, 509/544), CYP2C9*1 *2 (0.18%, 1/544), CYP2C9*1 *3 (5.88%, 32/544) and CYP2C9*1 *60 (0.37%, 2/544); while VKORC1 had three genotypes AA (82.72%, 450/544), GA (15.99%, 87/544) and GG (1.29%, 7/544). After reaching the anticoagulation index (INR 2.0-3.0), the steady-state dose of warfarin was the highest in patients with CYP2C9 *1/*1 and VKORC1 GA/GG genotypes, reaching (3.70±1.34) mg/d. The lowest steady-state dose of warfarin was (2.17±0.29)mg/d in patients with both new mutations ( F=22.09, P<0.001). Multiple linear regression analysis showed that body surface area, use of amiodarone, CYP2C9 and VKORC1 genotypes were the independent influencing factors of warfarin steady-state dose ( t=4.44, -2.90, -6.96, 2.14; P<0.05) and the steady-state dose prediction model of warfarin was established. Conclusion:Body weight, height, body surface area, gender, smoking, and combination of amiodarone may significantly affect the steady-state dose of warfarin in patients. CYP2C9 and VKORC1 mutant genotypes were significantly related to the steady-state dose of warfarin. The prediction model based on genetic factors and other influencing factors may effectively predict the steady-state dose of warfarin in Han patients with atrial fibrillation.