[Resistance to coumarin derivatives due to mutated vitamin-K enzyme].
In 2006 a case report was published in this journal describing partial acenocoumarol- and phenprocoumon resistance in a 78-year-old man. A mutation in the VKORC1 gene was suggested to be the cause of the observed resistance. We examined the patient and found a new and hitherto unknown mutation in the VKORC1 gene which may well explain the observed resistance. The mutation concerns a polymorphism in exon 2 that predicts the substitution of tryptophan at position 59 of the VKOR protein by arginine, the p.Trp59Arg mutation. Meanwhile, we have detected the same p.Trp59Arg mutation in another patient with coumarin derivative resistance. The fact that this mutation did not occur in 100 individuals who responded well to coumarin derivatives, together with the knowledge that amino acid 59 is conserved among species, renders it likely that p.Trp59Arg was the cause of the partial acenocoumarol- and phenprocoumon resistance observed in these two patients.
Jeroen Bosch Ziekenhuis, 's-Hertogenbosch, The Netherlands. m.hermans@jbz.nl
Mirjam H A
MH
Hermans
Jeroen
J
Poodt
J H H Anke
JH
van Geest-Daalderop
Nathalie C
NC
Péquériaux
Jean M H
JM
Conemans
D000925:Anticoagulants / Q000494:pharmacology*; D003374:Coumarins / Q000494:pharmacology*; D004351:Drug Resistance / Q000235:genetics*; D006801:Humans; D006899:Mixed Function Oxygenases / Q000235:genetics*; D020125:Mutation, Missense / Q000187:drug effects; D014812:Vitamin K / Q000378:metabolism; D064417:Vitamin K Epoxide Reductases
D000925:Anticoagulants; D003374:Coumarins; D014812:Vitamin K; C030123:coumarin; D006899:Mixed Function Oxygenases; C578523:VKORC1 protein, human; D064417:Vitamin K Epoxide Reductases