Polymorphisms of CYP2C9*2, CYP2C9*3 and VKORC1 genes related to time in therapeutic range in patients with atrial fibrillation using warfarin

Abstract

Maria Mariana Barros Melo da Silveira,1,2 Leiliandry de Araújo Melo,1,2 Filipe Maia Ferreira Gomes,1 Leonardo José de Cupertino Barreto da Rocha Andrade,1 Isabela Paulino Serur,1 Isabelle Cecília de Vasconcellos Piscoya,1 Raposo Marina Gueiros,1 Kleyton Palmeira do Ó,1 Raul Emídio de Lima,3 Victor Arthur Eulálio Brasileiro,1,2 Luydson Richardson Silva Vasconcelos,1,3 Dário Celestino Sobral Filho21Faculdade de Ciências Médicas, Universidade de Pernambuco - FCM/UPE, Recife, Brazil; 2Pronto Socorro Cardiológico Professor Luiz Tavares - PROCAPE/UPE, Recife, Brazil; 3Instituto Aggeu Magalhães - FIOCRUZ-PE, Recife, BrazilIntroduction: Warfarin continues to be the most widely used anticoagulant in clinical practice around the world for the prevention of thromboembolic events in patients with atrial fibrillation (AF). The evaluation of the quality of anticoagulation control, estimated by time in therapeutic range (TTR), is accepted as a good method to evaluate the quality of anticoagulation. The variability of TTR can be explained by the presence of variants of the CYP2C9 and VKORC1 genes.Methods: This study examined the association between polymorphisms of the CYP2C9 and VKORC1 genes and control of oral anticoagulation, through TTR, in patients with AF. A cross-sectional study was conducted within a cohort follow-up. The study comprised of 317 patients with AF, using warfarin, who were followed up for one year. The genotyping of genes CYP2C9 (rs1057910), (rs1799853) and VKORC1 (rs923231) was performed by PCR in real time, using TaqMan probes.Results: Patients who had variant genotypes for the CYP2C9*3 gene (rs1057910) presented higher TTR (TTR 81–100%) when compared to when compared to the <45% and 46–60% TTR groups (p=0.005 and p=0.002, respectively). Regarding VKORC1 (rs923231), patients who had the variant genotype for the VKORC1 (rs923231) gene also presented a higher TTR (TTR 81–100%), when when compared to the <45% and 46–60% TTR groups (p=0.005 and p=0.004, respectively). In a multivariate model, VKORC1 (rs923231) remained associated for comparisons with the TTR groups (<45% vs 81–100% groups, p=0.01; and 46–60% vs 81–100% groups, p=0.01).Conclusion: The genotypes of the CYP2C9*3 (AA) and VKORC1 -1639 (GG) genes were associated with the worst quality of anticoagulation control (TTR) in patients with AF using warfarin in the northeast of Brazil.Keywords: atrial fibrillation, time in therapeutic range, oral anticoagulant, genetic polymorphism

Keywords

• atrial fibrillation
• time in therapeutic range
• oral anticoagulant
• genetic polymorphism.