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1. J Thromb Haemost. 2012 Mar 12. doi: 10.1111/j.1538-7836.2012.04694.x. [Epub ahead
of print]

An evaluation of gene-gene interaction between the CYP2C9 and VKORC1 genotypes
affecting the anticoagulant effect of phenprocoumon and acenocoumarol.

van Schie RM, Babajeff AM, Schalekamp T, Wessels JA, le Cessie S, de Boer A, van
der Meer FJ, van Meegen E, Verhoef TI, Rosendaal FR, Maitland-van der Zee AH; for
the EU-PACT study group.

Department of Pharmacoepidemiology and Clinical Pharmacology, Utrecht Institute
for Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands
Department of Clinical Pharmacy & Toxicology, Leiden University Medical Center,
Leiden, The Netherlands Department of Medical Statistics and Bioinformatics,
Leiden University Medical Center, Leiden, The Netherlands Department of Clinical
Epidemiology, Leiden University Medical Center, Leiden, The Netherlands
Department of Thrombosis and Hemostasis, Leiden University Medical Center,
Leiden, The Netherlands Medial, medical-diagnostic laboratories, Hoofddorp, The
Netherlands The members of the EU-PACT study group are: A. de Boer, A.K. Daly, E.
Haschke-Becher, F. Kamali, V.G. Manolopoulos, M. Pirmohamed, W.K. Redekop, F.R.
Rosendaal, J. Stingl, M. Wadelius, A.H. Maitland- van der Zee.

Background: Previous studies provide contradictory results regarding the
interaction between CYP2C9 and VKORC1 genotypes affecting various outcome
measures. Objectives: We aimed to provide a definite answer regarding the
question whether there exists a gene-gene interaction between CYP2C9 and VKORC1
on the anticoagulant effect of phenprocoumon and acenocoumarol.
Patients/Methods: The EU-PACT cohort dataset which contains data on 624
phenprocoumon and 471 acenocoumarol patients was used. Patient characteristics,
pharmacogenetic data, INRs and dosages were available. We investigated whether
there was an interaction effect between the CYP2C9 and VKORC1 genotypes affecting
the maintenance dose, time to severe over-anticoagulation and time to achieve
stability during the first 180 days of phenprocoumon and acenocoumarol therapy in
addition to the effect of the separate genotypes. The interaction effect was
investigated by adding the product term of the CYP2C9 and VKORC1 genotype-classes
for 4 different commonly used CYP2C9 classifications to the linear regression
model -for the outcome measure maintenance dose- or to the Cox regression models
-for the outcome measures time to severe over-anticoagulation and time to achieve
stability-. Results: No significant interactions -all p-values above 0.23 for
phenprocoumon and 0.30 for acenocoumarol- were observed for all outcome measures.
Conclusions: There are no interactions between the CYP2C9 and VKORC1 genotypes
affecting the maintenance dose, time to severe overanticoagulation and time to
achieve stability for phenprocoumon and acenocoumarol. © 2012 International
Society on Thrombosis and Haemostasis.

© 2012 International Society on Thrombosis and Haemostasis.

PMID: 22409277 [PubMed - as supplied by publisher]