Jornal Vascular Brasileiro
https://www.jvascbras.org/article/doi/10.1590/1677-5449.200214
Jornal Vascular Brasileiro
Original Article

Polymorphism of the CYP2C9 and VKORC1 genes in patients on the public health system of a municipality in Southern Brazil

Polimorfismo dos genes CYO2C9 e VKORC1 em pacientes do Sistema Público de Saúde em um município do Sul do Brasil

Christiane Colet; Mariana Rodrigues Botton; Karin Hepp Schwambach; Tânia Alves Amador; Isabela Heineck

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Abstract

Abstract: Background: Genetic factors can be responsible for part of the populational and interindividual differences observed in warfarin users.

Objectives: To identify occurrence of polymorphisms of the CYP2C9 and VKORC1 genes in patients taking warfarin and relate these profiles to their medication dosages and the Time in Therapeutic Range (TTR).

Methods: Monthly interviews were conducted for data collection. Data were collected on demographic characteristics and medications in use, especially warfarin, including reason for prescription and weekly dose. TTR was calculated as the percentage of days with international normalized ratio (INR) between 2 and 3. The CYP2C9 and VKORC1 genes were analyzed at a Human Genetics Laboratory.

Results: 49 patients (74.2%) had polymorphisms of the CYP2C9 and/or VKORC1 genes; the remaining 17 (25.8%) did not have these polymorphisms. The average weekly dose of warfarin was lower among those who had a polymorphism for any of the genes compared to those who did not, with a significant difference (p = 0.035). The mean TTR was also lower among patients with polymorphism. However, the difference between the two groups was not significant for this variable (p = 0.438).

Conclusions: An association was observed between the polymorphisms and the warfarin doses taken by the patients. However, there was no association with adverse events or the time spent within the therapeutic range in this sample.

Keywords

warfarin, genetic polymorphism, adverse effects

Resumo

Resumo: Contexto: Fatores genéticos podem ser responsáveis por parte das diferenças populacionais e interindividuais observadas em usuários de varfarina.

Objetivos: Identificar a ocorrência de polimorfismo dos genes CYP2C9 e VKORC1 em pacientes em uso de varfarina e relacionar esses perfis com a dose do medicamento e o tempo no intervalo terapêutico.

Métodos: Foram realizadas entrevistas mensais para a coleta de dados. Foram reunidos dados sobre características demográficas e medicamentos em uso, principalmente sobre varfarina, como motivo da prescrição e dose semanal. O tempo no intervalo terapêutico foi calculado como a porcentagem de dias com razão normalizada internacional entre os valores 2 e 3. Os genes CYP2C9 e VKORC1 foram analisados em laboratório de Genética Humana.

Resultados: Entre os participantes, 49 pacientes (74,2%) apresentaram polimorfismo dos genes CYP2C9 e/ou VKORC1; os 17 restantes (25,8%) não apresentaram esses polimorfismos. A dose média semanal de varfarina foi menor entre os que apresentaram polimorfismo para algum dos genes em comparação aos que não apresentaram, com diferença significativa (p = 0,035). O tempo no intervalo terapêutico médio também foi menor entre os pacientes com polimorfismo. Porém, não houve diferença significativa entre os dois grupos para essa variável (p = 0,438).

Conclusões: Foi observada associação entre os polimorfismos e a dose de varfarina utilizada pelos pacientes; no entanto, não houve associação com eventos adversos e o tempo de permanência na faixa terapêutica nessa amostra.
 

Palavras-chave

varfarina, polimorfismo genético, efeitos adversos

References

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Submitted date:
12/01/2020

Accepted date:
01/31/2021

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