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Dicumarinic oral anticoagulants have a  narrow therapeutic range and a great individual variability in response, which  makes calculation of the correct dose difficult and critical. Genetic factors  involved in this variability include polymorphisms of genes that encode the  metabolic enzyme CYP2C9 and the target enzyme vitamin K epoxide reductase  complex 1 (VKORC1); these polymorphisms can be associated with reduced  enzymatic expression. We examined the frequency of the most relevant variants  encoding CYP2C9 (alleles *1, *2 and *3) and VKORC1 (SNP -1639A&gt;G) in the  Argentinian population. Molecular typing was performed by PCR-RFLP on a  randomly selected sample of 101 healthy volunteers from the Hospital Italiano  de Buenos Aires gene bank. Fifty-seven subjects were identified as homozygous  for CYP2C9*1 and 14 for *2, while 24 and 5 were heterozygous for *2 and *3  alleles; one individual was a composite heterozygote (*2/*3). When we examined  VKORC1, 21 subjects were AA homozygous, 60 were AG heterozygotes and 20 were GG  homozygotes. This is the first analysis of genotypic frequencies for CYP2C9 and  VKORC1 performed in an Argentinian population. These allele prevalences are  similar to what is known for Caucasian population, reflecting the European  ancestor of our patient population, coming mostly from Buenos Aires city and  surroundings. Knowledge of this prevalence information is instrumental for  cost-effective pharmacogenomic testing in patients undergoing oral  anticoagulation treatment.

Prevalence of CYP2C9 and VKORC1 alleles in the Argentine population and implications for prescribing dosages of anticoagulants