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Algorithm for predicting low maintenance doses of warfarin using age and polymorphisms in genes CYP2C9 and VKORC1 in Brazilian subjects

The Pharmacogenomics Journal volume 20, pages 104–113 (2020)Cite this article

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Abstract

Warfarin exhibits a wide variation in dose requirements. We sought to evaluate the association of polymorphisms CYP2C9*2 (rs1799853), CYP2C9*3 (rs1075910), and VKORC1-G1639A (rs9923231) and nongenetic factors with maintenance doses of warfarin <17.5 mg/week and to create an algorithm to predict drug sensitivity. This is a retrospective cohort study including 312 patients assisted at an anticoagulation clinic in Brazil. The mean age of participants was 60.4 ± 13.5 years and 59.9% were female. The logistic regression model included: age [odds ratio (OR) 1.03, 95% confidence interval (CI) 1.01–1.06], genotype VKORC1 AA (OR 31.61, 95% CI 11.20–100.15) and genotype CYP2C9 2/2, 2/3 or 3/3 (OR 16.48, 95% CI 3.37–81.79). The creation of our algorithm involved warfarin-experienced patients on stable doses, identifying factors associated with drug sensitivity. The validation of this algorithm allows its use in future populations to determine the initial dose distinguishing patients with dose requirements <17.5 mg and reducing time to achieve stable doses.

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Acknowledgements

This study was partially supported by the Programa de Pós-graduação em Ciências da Saúde: Infectologia e Medicina Tropical of the Universidade Federal de Minas Gerais, the Pró-Reitoria de Pesquisa da Universidade Federal de Minas Gerais and the Fundação de Amparo à Pesquisa de Minas Gerais (FAPEMIG). MOCR, RPS, and KBG are researchers of the Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq).

Author contributions

AOMM, MOCR, DDR, and MAPM have designed the study. AOMM collected data. AOMM, EIFC, and KGB performed genotyping assays. AOMM, RPS, EAR, and MAPM planned and conducted statistical analysis. AOMM, MOCR, DDR, MAPM, and KGB assisted in interpreting the results. AOMM drafted the first version of the study protocol. All authors have provided relevant contributions to drafting, editing, and revising this manuscript.

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Authors and Affiliations

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

    Aline de Oliveira Magalhães Mourão, Emílio Itamar de Freitas Campos, Manoel Otávio da Costa Rocha & Maria Auxiliadora Parreiras Martins

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

    Karina Braga Gomes, Edna Afonso Reis & Maria Auxiliadora Parreiras Martins

  3. Instituto de Ciências Exatas, Universidade Federal de Minas Gerais, Av. Pres. Antônio Carlos, 6627, Pampulha, Belo Horizonte, Minas Gerais, 31270-901, Brazil

    Edna Afonso Reis

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

    Renan Pedra de Souza

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

    Daniel Dias Ribeiro, Manoel Otávio da Costa Rocha & Maria Auxiliadora Parreiras Martins

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  1. Aline de Oliveira Magalhães Mourão
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Correspondence to Maria Auxiliadora Parreiras Martins.

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de Oliveira Magalhães Mourão, A., Braga Gomes, K., Afonso Reis, E. et al. Algorithm for predicting low maintenance doses of warfarin using age and polymorphisms in genes CYP2C9 and VKORC1 in Brazilian subjects. Pharmacogenomics J 20, 104–113 (2020). https://doi.org/10.1038/s41397-019-0091-3

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