Abstract

There is no strong evidence on pharmacogenetics role on the quality of INR control after the initiation phase and on the maintenance of stable INR on the long term as measured by the time in therapeutic range (TTR). The benefit of a score such as SAMe-TT2R2 is that it can preemptively guide clinicians on whether to start the patient on warfarin or direct oral anticoagulant. To determine the association between genetic variants in CYP2C9, VKORC1, and CYP4F2 and TTR. To validate SAMe-TT2R2 score predictive ability on the quality of anticoagulation in Qatari patients. This is an observational nested case–control study that was conducted on a cohort of Qatari patients treated with warfarin with previously identified genotype for the CYP2C9, VKORC1, and CYP2F4. The sample size of this cohort was 148 patients. Mean TTR was 62.7 ± 21%. TTR was not significantly different among carriers of the CYP2C9*2 &*3, VKORC1(–1639G>A) or CYP4F2*3 compared to their non-carriers alleles. None of the factors in the SAMe-TT2R2 score had a significant effect on the TTR except for the female gender where TTR was significantly lower in females (n = 89) compared to males (n = 59) (59.6 ± 21% vs. 67.2 ± 20%, p = 0.03). Furthermore, patients with SAMe-TT2R2 score of zero had significantly better TTR compared to those with higher scores (76.5 ± 17% vs. 61.8 ± 21%, p = 0.04). Logistic regression analysis showed that high SAMe-TT2R2 score was the only statistically significant predicting factor of poor INR control (odds ratio (OR) 5.7, 95% confidence interval (CI) 1.1–28.3, p = 0.034). Genetic variants have no contribution to the quality of INR control. SAMe-TT2R2 score was predictive for the poor quality of anticoagulation in a cohort of Qatari patients.

Highlights

  • For over 60 years, warfarin has been the mainstay anticoagulant used in the prevention and treatment of thromboembolic complications in patients with atrial fibrillation, venous thromboembolism, prosthetic heart valves, and coronary artery disease [1]

  • An important result from this study is that cytochrome p450 2C9 (CYP2C9), vitamin K epoxide reductase complex subunit-1 (VKORC1), and CYP2F4 genetic mutations are not associated with the quality of anticoagulation during maintenance phase in a cohort of Qatari warfarin patients

  • In 2015, Park and colleagues collected data from 380 Korean patients with atrial fibrillation and evaluated genetic (CYP2C9 and VKORC1) and non-genetic (SAMe-TT2R2 score) factors associated with therapeutic range (TTR) [33]

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Summary

Introduction

For over 60 years, warfarin has been the mainstay anticoagulant used in the prevention and treatment of thromboembolic complications in patients with atrial fibrillation, venous thromboembolism, prosthetic heart valves, and coronary artery disease [1]. Several studies showed the considerable contribution of genetic variants in the genes encoding vitamin K epoxide reductase complex subunit-1 (VKORC1) and cytochrome p450 2C9 (CYP2C9) in warfarin dose variability. This contribution differs from one population to another depending on the allele frequencies for every population [6,7,8,9]. In recent work from our group on the effect of genetic polymorphisms on warfarin stable dose in Qatari patients, we have shown that CYP2C9 and VKORC1 polymorphism accounted for 10.4% and 14.8% of warfarin dose variability, respectively [10]

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