Why the study?
Genetic factors can account for populational and interindividual differences among warfarin users, prompting evaluation of CYP2C9 and VKORC1 polymorphisms and their relationship with medication dosages and time in therapeutic range.
Does the presence of CYP2C9 and/or VKORC1 polymorphisms affect warfarin dosage and Time in Therapeutic Range in patients taking warfarin?
Does the presence of CYP2C9 and/or VKORC1 polymorphisms affect warfarin dosage and Time in Therapeutic Range in patients taking warfarin?
CYP2C9 and VKORC1 polymorphisms are associated with lower required warfarin doses but do not significantly impact the time in therapeutic range or adverse events.
Association of CYP2C9/VKORC1 variants with warfarin dose but not TTR; leaves open utility of genotyping for dose prediction in this setting.
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.
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Colet et al. (2021) studied this question.
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