Blood Reviews
Volume 22, Issue 3 , Pages 127-140, May 2008

Oral anticoagulants: Pharmacogenetics:

Relationship between genetic and non-genetic factors

  • Giovanna D’Andrea

      Affiliations

    • Genetica Medica, Dipartimento di Scienze Biomediche, Università di Foggia, Italy
  • ,
  • Rosa D’Ambrosio

      Affiliations

    • Genetica Medica, Dipartimento di Scienze Biomediche, Università di Foggia, Italy
  • ,
  • Maurizio Margaglione

      Affiliations

    • Genetica Medica, Dipartimento di Scienze Biomediche, Università di Foggia, Italy
    • Unita’ di Emostasi e Trombosi, I.R.C.C.S. “Casa Sollievo della Sofferenza”, S. Giovanni Rotondo, Italy
    • Corresponding Author InformationCorresponding author.

published online 31 January 2008.

Summary 

Oral anticoagulants, the main drugs used for the prevention and treatment of thromboembolic diseases, exhibit a greater than 10-fold inter-individual variability in the dose requirement to achieve a therapeutic response. The relationship between the dose prescribed and the individual response is regulated by genetic and environmental factors. In particularly, molecular analysis of two genes, encoding for the enzyme responsible for the warfarin (S)-isoform catabolism (CYP2C9) and for the target enzyme vitamin K epoxide reductase complex 1 (VKORC1), strongly suggested that their genetic variations greatly affect the individual response to oral anticoagulants. Genotype based modelling explained a large amount of dose-variations. As a perspective, it appears meaningful to increase the number of candidate genes involved in the metabolism of oral anticoagulants to set up a powerful tool, easy for a rapid use into all laboratories and clinical settings, to improve the oral anticoagulants therapy management.

Keywords: Warfarin, VKORC1, CYP2C9, Gene mutation, Pharmacogenetics

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PII: S0268-960X(07)00073-2

doi:10.1016/j.blre.2007.11.004

Blood Reviews
Volume 22, Issue 3 , Pages 127-140, May 2008