Allelic variants in the CYP2C9 and VKORC1 loci and interindividual variability in the anticoagulant dose effect of warfarin in Italians.

Introduction: Warfarin is currently considered to be the anticoagulant of choice in the long-term treatment and prevention of thromboembolic events. However, it presents a narrow therapeutic range and a great interindividual dose variability. We investigated the influence of variants of the VKORC1 and CYP2C9 loci on the mean weekly warfarin dose (MWWD) required to reach stabilized therapeutic international normalized ratio, in order to confirm and to estimate the contribution of common genetic variability of these two genes in an Italian population and to search for novel rare VKORC1 alleles. Methods: A total of 148 patients were followed for 6 months and analyzed for VKORC1 and CYP2C9 gene variants. Analysis of variance and multiple linear regression analysis were used to study the contribution of each genetic factor to MWWD requirement. Results: The complete sequencing of the VKORC1 coding region did not reveal the presence of exonic variants, while two common noncoding SNPs were highly associated: the ...