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Pharmakogenetik der oralen Antikoagulation mit Cumarinen

Pharmacogenetics of oral anticoagulation therapy with coumarins

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medizinische genetik

Zusammenfassung

Die Klonierung des VKORC1-Gens hat maßgeblich zu einem besseren Verständnis des Vitamin-K-Zyklus beigetragen. Das VKORC1-Protein konnte als der molekulare Zielort (Target) der Cumarine identifiziert werden. Mutationen und SNP innerhalb der translatierten und nichttranslatierten Regionen des VKORC1-Gens verursachen eine partielle bis totale Cumarinresistenz oder -sensitivität. Die Verfügbarkeit einer molekulargenetischen Diagnostik (VKORC1, CYP2C9) und einer Laboranalytik mittels HPLC (zur Bestimmung des Cumarin-, Vitamin-K- und Vitamin-K-Epoxid-Spiegels) ist hilfreich in der Detektion hereditärer und erworbener Einflussgrößen der Cumarintherapie und könnte zukünftig für eine individualisierte, risikoärmere orale Antikoagulationstherapie zum Einsatz kommen.

Abstract

The recent identification of VKORC1 has made important contributions to our understanding of the vitamin K cycle. The VKORC1 enzyme was shown to be the molecular target of coumarin drugs. Mutations and polymorphisms in coding and noncoding regions of the VKORC1 gene have been shown to cause both a partial to total coumarin resistance and coumarin sensitivity. Availability of molecular diagnostics (VKORC1, CYP2C9) and drug monitoring by HCPLC (determination of coumarin, vitamin K, and vitamin K epoxide levels) is helpful for detecting hereditary and acquired factors influencing coumarin therapy. In the future, these tools may be instrumental in designing individualized oral anticoagulation therapy regimens.

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Abb. 1

Notes

  1. Die INR ist ein standardisierter Wert für die Gerinnungszeit des Blutes, mit dem die Effektivität einer Antikoagulationstherapie bestimmt werden kann. Während der Normalwert definitionsgemäß bei 1,0 liegt, sollte durch die Cumarinbehandlung eine Verzögerung der Gerinnung angestrebt werden, die bei einem INR=2,0–3,0 erreicht wird.

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Authors and Affiliations

  1. Institut für Experimentelle Hämatologie und Transfusionsmedizin, Universitätsklinik Bonn, Sigmund-Freud-Straße 25, 53127, Bonn, Deutschland

    J. Oldenburg, H. Seidel & M. Watzka

  2. Institut für Humangenetik, Biozentrum, Universität Würzburg, Würzburg, Deutschland

    S. Rost  & C.R. Müller-Reible

Authors
  1. J. Oldenburg
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  2. S. Rost
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  3. H. Seidel
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  4. M. Watzka
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  5. C.R. Müller-Reible
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Correspondence to J. Oldenburg.

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Oldenburg, J., Rost , S., Seidel, H. et al. Pharmakogenetik der oralen Antikoagulation mit Cumarinen. medgen 20, 230–235 (2008). https://doi.org/10.1007/s11825-008-0095-x

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  • DOI: https://doi.org/10.1007/s11825-008-0095-x

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