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Irish Journal of Medical Science

, Volume 177, Issue 2, pp 159–161 | Cite as

A vitamin K epoxide reductase complex subunit 1 mutation in an Irish patient with warfarin resistance

  • F. N. Áinle
  • A.  Mumford
  • E. Tallon
  • D. McCarthy
  • K. Murphy
Case Report

Abstract

Background

Oral anticoagulant use continues to increase rapidly. In this setting, it is important to recognise that some normal individuals can demonstrate resistance to anticoagulation with warfarin. Such patients require high daily doses of warfarin (>20 mg) in order to maintain an international normalised ratio (INR) within the target therapeutic range (2–3). We describe the case of an elderly gentleman with atrial fibrillation who demonstrated true warfarin resistance.

Methods

We performed vitamin K epoxide reductase subunit 1 (VKORC1) gene coding sequence analysis using polymerase chain reaction primers.

Results

We demonstrated that our patient was heterozygous for a 383 T→G transition in exon 2 of the VKORC1 gene.

Conclusions

This is the first documented Irish case of true warfarin resistance as a result of a mutation in VKORC1, a novel gene encoding a component of the epoxide reductase enzyme complex which is an essential component in the recycling pathway of vitamin K and is postulated to be one of the sites of action of warfarin.

Keywords

Anticoagulant clinics Coumarins VKORC1 mutations Warfarin resistance 

Notes

Acknowledgments

We wish to thank the staff of the coagulation laboratory of St Vincent’s University Hospital, Elm Park, Dublin.

References

  1. 1.
    Suttie JW (1987) The biochemical basis of warfarin therapy. Adv Exp Med Biol 214:3–16PubMedGoogle Scholar
  2. 2.
    Li T, Chang CY, Jin DY, Lin PJ, Khvorova A, Stafford DW (2004) Identification of the gene for vitamin K epoxide reductase. Nature 427(6974):541–4PubMedCrossRefGoogle Scholar
  3. 3.
    Rost S, Fregin A, Ivaskevicius V et al (2004) Mutations in VKORC1 cause warfarin resistance and multiple coagulation factor deficiency type 2. Nature 427(6974):537–41PubMedCrossRefGoogle Scholar
  4. 4.
    Meyer UA (2000) Pharmacogenetics and adverse drug reactions. Lancet 356(9242):1667–71PubMedCrossRefGoogle Scholar
  5. 5.
    Harrington DJ, Underwood S, Morse C, Shearer MJ, Tuddenham EG, Mumford AD (2005) Pharmacodynamic resistance to warfarin associated with a Val66Met substitution in vitamin K epoxide reductase complex subunit 1. Thromb Haemost 93(1):23–6PubMedGoogle Scholar
  6. 6.
    O’Reilly RA, Aggeler PM, Hoag MS, Leong LS, Kropatkin ML (1964) Hereditary transmission of exceptional resistance to coumarin anticoagulant drugs. The first reported kindred. N Engl J Med 271:809–15PubMedCrossRefGoogle Scholar
  7. 7.
    Bodin L, Horellou MH, Flaujac C, Loriot MA, Samama MM (2005) A vitamin K epoxide reductase complex subunit-1 (VKORC1) mutation in a patient with vitamin K antagonist resistance. J Thromb Haemost 3(7):1533–5PubMedCrossRefGoogle Scholar

Copyright information

© Royal Academy of Medicine in Ireland 2008

Authors and Affiliations

  • F. N. Áinle
    • 1
  • A.  Mumford
    • 2
  • E. Tallon
    • 1
  • D. McCarthy
    • 1
  • K. Murphy
    • 1
  1. 1.Department of HaematologySt Vincent’s HospitalDublin 20Ireland
  2. 2.Department of HaematologyBristol Royal InfirmaryBristolUK

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