Warfarin is the most widely used oral anticoagulant in the world for patients 
with venous thrombosis, pulmonary embolism, chronic atrial fibrillation, and 
prosthetic heart valves. Approximately 30 genes contribute to therapeutic 
effects of warfarin, and genetic polymorphisms in these genes may modulate its 
anticoagulant activity. In contrast to monogenic pharmacogenetic traits, 
warfarin drug response is a polygenic trait, and development of diagnostic tools 
predictive of adverse reactions to warfarin requires a novel approach. A 
combination of two strategies, biochemical isolation of allelic variants and 
linkage disequilibrium association studies, was used to find an association 
between genetic polymorphisms in the candidate genes and warfarin response. A 
strong association was found between genetic polymorphisms in six genes, 
including VKORC1, CYP2C9, PROC, EPHX1, GGCX, and ORM1, and interindividual 
variability in the anticoagulant effect of warfarin; the strongest predictors 
were VKORC1 and CYP2C9. Generation of single nucleotide polymorphism (SNP)-based 
dense genetic maps made it possible to identify haplotypes associated with 
drugresponse phenotypes. Discrimination between haplotypes associated with 
warfarin dose phenotypes can be achieved by a limited set of informative 
polymorphisms (tag SNPs). The use of tag SNPs in pharmacogenomic analysis 
provides a promising tool for dissecting polygenic traits of drug response.