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Evaluation of the effect of SNPs in CYP3A4 and CYP4F2 on the stable phenprocoumon and acenocoumarol maintenance dose.

J Thromb Haemost. 2013 Mar 19;

Authors: van Schie RM, Aoussar A, van der Meer FJ, de Boer A, van der Zee AH


Coumarins have a narrow therapeutic window and there is wide inter- and intra-individual variability in dose requirements. Genetic factors explain the largest part of the inter-individual variability in dose requirements [1,2]. Especially polymorphisms in the VKORC1 and CYP2C9 gene influence coumarin dose requirements. However, SNPs in CYP3A4, a metabolizing enzyme of coumarins, mainly phenprocoumon, and CYP4F2, the metabolizing enzyme of vitamin K, might affect dose requirements as well. Two studies with small sample sizes investigated the effect of the most common variant allele CYP3A4*1B genotypes on the phenprocoumon dose and acenocoumarol dose [3,4] and did not find an association. The recently identified functional SNP CYP3A4*22[5] is associated with decreased CYP3A4 activity and increased nephrotoxicity of the typical CYP3A4 substrate cyclosporine [6]. © 2013 International Society on Thrombosis and Haemostasis.

PMID: 23510058 [PubMed - as supplied by publisher]