VKORC1 and CYP2C9 allelic variants influence acenocoumarol dose requirements in Greek patients.

AIM

To identify the frequencies of the polymorphisms CYP2C92, CYP2C93 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: CYP2C92 (Arg144Cys), CYP2C93 (Ile359Leu) and VKORC1-1639G>A allelic variants were analyzed in 98 patients treated with acenocoumarol.

RESULTS

Allelic frequencies of CYP2C92, CYP2C93 and VKORC1A were found to be 0.155, 0.075 and 0.485, respectively. Carriership of at least one CYP2C93 allele led to the most pronounced reduction in the required mean dose (p<0.0001). In contrast, the CYP2C92 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, CYP2C92 and CYP2C93 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.