Resumo

RAGGIO, VíCTOR et al. Variantes de los genes CYP2C9 y apolipoproteína E en la respuesta individual a la warfarina. Rev.Urug.Cardiol. [online]. 2006, vol.21, n.2, pp.104-116. ISSN 1688-0420.

SUMMARY Introduction: warfarin is the most frequently used oral anticoagulant in Uruguay and worldwide. Polymorphic variants in various genes modulate individual response to this drug, especially CYP2C9. We studied the influence of these genetic variants on interindividual variability in response to warfarin and the risk of adverse reactions in an uruguayan population. Materials and methods: the study involved 55 patients undergoing chronic oral anticoagulant treatment with warfarin. Data on daily maintenance dose, pharmacokinetic response and adverse reactions was collected. CYP2C9 *1, *2 and *3, and Apoe E2, E3 and E4, genotype was determined by standard procedures. Results: carriers of CYP2C9 *3 allele required the lesser manteinance dose, followed by *2 allele carriers and then *1 homocygotes (p=0.049). CYP2C9 *3 allele carriers had more episodes of above de range International Normalized Ratio and required more dose adjustments to achieve a proper anticoagulation; adverse events were more frequent in patients with CYP2C9 *1/*3, regarding bleeding events as wells as overanticoagulation. Presence of ApoE E4 allele is associated with a  moderately elevated sensibility to warfarin. Conclusions: this study is the first carried out on this subjet in an uruguayan population and confirms an increased sensibility to warfarin and risk of adverse effects  in carriers of CYP2C9 *3 allele and in carriers of ApoE E4 variant, wich could be useful in warfarin dose and risk individualization during treatment with this drug. Genotypic data should be considered when establishing the best individual dose for individuals at high risk of bleeding, in those who suffered an adverse effect with this drug for physiopathlogic diagnosis and in young patients who underwent cardiac surgery who would potentially face a long term anticoagulant therapy. We will continue evaluating genomic components of risk during anticoagulation

Palavras-chave : GENES; WARFARIN; APOLIPOPROTEINS E; DOSE RESPONSE; RELATIONSHIP, DRUG.

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