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

AIM: To identify the frequencies of the polymorphisms CYP2C9*2, CYP2C9*3 and VKORC1-1639 G>A in the Greek population and investigate whether these polymorphisms and patient demographics (age, sex and comedication) could explain the interindividual variability of acenocoumarol dose requirements for efficient anticoagulation. MATERIALS & METHODS: CYP2C9*2 (Arg144Cys), CYP2C9*3 (Ile359Leu) and VKORC1-1639G>A allelic variants were analyzed in 98 patients treated with acenocoumarol. RESULTS: Allelic frequencies of CYP2C9*2, CYP2C9*3 and VKORC1A were found to be 0.155, 0.075 and 0.485, respectively. Carriership of at least one CYP2C9*3 allele led to the most pronounced reduction in the required mean dose (p<0.0001). In contrast, the CYP2C9*2 allele played a minor role (p=0.3). VKORC1 A/A patients needed approximately a third of the dose required by wild-type patients to achieve the target INR (p<0.0001). Age was the only demographical factor significantly affecting acenocoumarol dose (p<0.0001). In a multivariable regression model, CYP2C9, VKORC1 genotypes and age explained 55% of acenocoumarol dosing variability. CONCLUSION: 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.