Influence of polymorphisms in CYP2C9, VKORC1, MDR1 and APOE genes on the warfarin maintenance dose in Brazilian patients

Author:

de Freitas Campos Emílio Itamar1,Gomes Karina Braga2ORCID,Ribeiro Daniel Dias3,Puurunen Marja Kaarina4,Oliveira Magalhães Mourão Aline de1,Ferreira Isadora Gonçalves2,da Costa Rocha Manoel Otávio13,de Souza Renan Pedra5ORCID,Parreiras Martins Maria Auxiliadora123ORCID

Affiliation:

1. Faculdade de Medicina, Universidade Federal de Minas Gerais, Av. Prof. Alfredo Balena, 190, Santa Efigênia, Belo Horizonte, Minas Gerais, 30130-100, Brasil

2. Faculdade de Farmácia, Universidade Federal de Minas Gerais, Av. Pres. Antônio Carlos, 6627, Pampulha, Belo Horizonte, Minas Gerais, 31270-901, Brasil

3. Hospital das Clínicas, Universidade Federal de Minas Gerais, Av. Prof. Alfredo Balena, 110, Santa Efigênia, Belo Horizonte, Minas Gerais, 30130-100, Brasil

4. Boston University, 73 Mount Wayte Avenue, Suite 2, Framingham, MA 01702, USA

5. Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Av. Pres. Antônio Carlos, 6627, Pampulha, Belo Horizonte, Minas Gerais, 31270-901, Brasil

Abstract

Background: Polymorphisms in the CYP2C9, VKORC1, MDR1 and APOE genes may impact warfarin dose. Aim: To investigate the influence of sociodemographic, clinical factors and polymorphisms *1, *2 and *3 for CYP2C9, -1639G>A for VKORC1, 3435C>T for MDR1, and ϵ2, ϵ3 and ϵ4 for APOE genes on the mean weekly warfarin maintenance dose in adults. Methods: This cross-sectional study recruited a calculated sample of 315 patients in three anticoagulation clinics in Brazil. A model containing the variables significantly associated with warfarin dose was estimated. Results: The mean age of patients was 64.1 ± 13.1 years, with 173 (54.9%) women. Age, use of amiodarone, genotype VKORC1 GA, genotype VKORC1 AA, genotypes CYP2C9*1/*2 or *1/*3 and genotypes CYP2C9*2/*2 or *2/*3 or *3/*3 were associated with a reduced warfarin dose. Conclusion: This study pointed out factors that could impact the management of oral anticoagulation.

Funder

CAPES

Publisher

Future Medicine Ltd

Subject

Pharmacology,Genetics,Molecular Medicine

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