Abstract
To assess allele frequency and potential predictive value of recurrent polymorphisms affecting warfarin metabolism in an unselected patient cohort attending an anticoagulant clinic (n=186). Genotyping of ten SNPs in five candidate genes (VKORC1, CYP2C9, CALU, EPHX and GGCX) was carried out by ABI PRISM SNaPshot multiplex method. We confirm the association between high-frequency SNPs, VKORC1 c.-1639G>A and CYP2C9 *2/*3 and warfarin sensitivity, and contribute additional evidence that the VKORC1 p.Asp36Tyr variant is recurrent and independently associated with warfarin resistance in our population. Other SNPs made little contribution. Warfarin sensitivity was predicted by known VKORC1 and CYP2C9 SNPs. However, resistance associated with p.Asp36Tyr in VKORC1 would not be predicted by the usual markers. Despite its relatively low frequency (3/186 or 1.6%) clinical considerations may warrant its inclusion in pharmacogenetic screening for initial warfarin dosing in clinic populations with a heterogeneous population base.
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