Worldwide allele frequency distribution of four polymorphisms associated with warfarin dose requirements
Copyright policy )Worldwide allele frequency distribution of four polymorphisms associated with warfarin dose requirements
The aim of the study is to improve our understanding of the worldwide allele frequency distribution of four genetic polymorphisms known to influence warfarin dosing (VKORC1 rs9923231, CYP2C9 rs1799853, CYP2C9 rs1057910 and CYP4F2 rs2108622). These four polymorphisms were genotyped in the Human Genome Diversity Project-Centre Etude Polymorphism Humain (HGDP-CEPH) worldwide sample (N=963), as well as in a sample of individuals of European, East Asian and South Asian ancestry living in Canada (N=316). The VKORC1 rs9923231 single nucleotide polymorphism (SNP) showed an extensive geographic differentiation, with the derived T allele appearing at very high allele frequencies in East Asian populations. Results from several tests of positive selection indicate that this unusual distribution may be the result of positive selection in East Asia. Understanding the worldwide distribution of markers determining warfarin dosing is important for the future application of pharmacogenomic-based algorithms to different population groups.
- University of Toronto Canada
- Instituto Nacional do Câncer Brazil
- University of Mary United States
- University of Washington United States
Polymorphism, Genetic, Genotype, Genome, Human, Sequence Analysis, DNA, Polymorphism, Single Nucleotide, Mixed Function Oxygenases, Cytochrome P-450 Enzyme System, Pharmacogenetics, Multigene Family, Vitamin K Epoxide Reductases, Ethnicity, Humans, Aryl Hydrocarbon Hydroxylases, Cytochrome P450 Family 4, Warfarin, Alleles, Cytochrome P-450 CYP2C9, Oligonucleotide Array Sequence Analysis
Polymorphism, Genetic, Genotype, Genome, Human, Sequence Analysis, DNA, Polymorphism, Single Nucleotide, Mixed Function Oxygenases, Cytochrome P-450 Enzyme System, Pharmacogenetics, Multigene Family, Vitamin K Epoxide Reductases, Ethnicity, Humans, Aryl Hydrocarbon Hydroxylases, Cytochrome P450 Family 4, Warfarin, Alleles, Cytochrome P-450 CYP2C9, Oligonucleotide Array Sequence Analysis
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