VKORC1 and CYP2C9 Allelic Variants Influence Acenocoumarol Dose Requirements in Greek Patients

Abstract

VKORC1-1639G>A, CYP2C9*2 and CYP2C9*3 polymorphisms were found to predispose to acenocoumarol sensitivity in Greeks. Other hereditary and nongenetic parameters must be incorporated in an individualized dosing algorithm to achieve a safer anticoagulant effect.

Acenocoumarol Pharmacogenetic Dosing Algorithms and Their Application in Two Bulgarian Patients with Low Anticoagulant Requirements

“…We searched the pharmacogenetics-based models including clinical and genetic data by Pub Med and identified eight pharmacogenetic acenocoumarol dosing algorithms (Borobia et al 2012;Cerezo-Manchado et al 2013;Krishna Kumar et al 2013;Markatos et al 2008;Pop et al 2013;Rathore et al 2012;van Schie et al 2011;Wolkanin-Bartnik et al 2013). They included both clinical variables (such as age, gender, BMI, and others) and genetic factors such as polymorphic variants in the genes CYP2C9, VKORC1, ApoE, and CYP4F2.…”

“…There are many pharmacogenetic algorithms, previously developed for warfarin in different population groups Huang et al 2009;Mazzaccara et al 2013;Miao et al 2007;Pathare et al 2012;Tham et al 2006;Wei et al 2012), but these for acenocoumarol are considerably less and insufficient (Borobia et al 2012;Cerezo-Manchado et al 2013;Krishna Kumar et al 2013;Markatos et al Table 4 The results from genotyping of selected polymorphic variants in both Bulgarian patients . We used univariate and multivariate linear regression analyses to evaluate major genetic and non-genetic factors and their influence on maintenance of daily dose acenocoumarol in studied cohort of patients.…”

“…The main differences between the algorithms are presented in Table 2. The first dosing algorithm for prediction of an optimal maintenance dose of acenocoumarol was published in 2008 by Markatos et al (Markatos et al 2008). The algorithm was developed for the Greek population and included the genotypes of polymorphic variants in CYP2C9 and VKORC1 genes as genetic factors and only age as a clinical factor.…”

“…The study was retrospective and was conducted in 98 patients receiving oral anticoagulant treatment. According to the authors, the limitations of the study are its retrospective character, the small sample size and the heterogeneity in age and cause of anticoagulation (Markatos et al 2008).…”

Extrapolation of acenocoumarol pharmacogenetic algorithms

“…Considerable research has been published on pharmacogenetic dosing algorithms designed to predict the individualized stable dose according to clinical and genetic factors, especially for warfarin [9,[13][14][15][16]19,21,34,47,49]. Algorithms for ACN have been less well developed and have focused on Caucasian populations [4,10,26,29,44,48], with the exception of two models for Indian patients [22,29]. The main indications for the application of ACN algorithms have been AF, VTE, and HVR [4,10,22,26,29,44,48].…”