AIMS The study aims to evaluate the impact of genetic, demographic and clinical data on various measures of outcome of anticoagulation quality in patients. PATIENTS AND METHODS The study consisted of 310 patients receiving long-term oral anticoagulation therapy in our hospital. Apart from demographic and clinical variables, 21 SNPs (in 7 genes) were analyzed and compared with the outcomes of ...

Warfarin dose requirements have been associated with 2 main haplotypes in VKORC1, but the responsible polymorphisms remain unknown. To search for regulatory polymorphisms, we measured allelic mRNA expression of VKORC1 in human liver, heart, and B lymphocytes. The observed 2-fold allelic mRNA expression imbalance narrowed possible candidate SNPs to -1639G>A and 1173C<T. This genotype effect was ...

Warfarin is a commonly used anticoagulant, whose dose needs to be determined for each individual patient owing to large inter-individual variability in its therapeutic dose. Although several clinical and genetic variables influencing warfarin dose have been identified, uncovering additional factors are critically important for safer use of warfarin. Through a genome-wide association study, we i...

QUESTION UNDER STUDY Prospective validation of two algorithms for the initiation of phenprocoumon treatment. METHODS Inpatients with new-onset anticoagulation were randomised to one of two computer assisted dosing algorithms, or to a control arm. The primary outcome measure was the time to achieve therapeutic anticoagulation without overshooting (INR >4.0 within 10 days). Secondary outcomes i...

BACKGROUND Rodenticide resistance to anticoagulants in Rattus norvegicus will lead to increased difficulties in combating these pest animals. Here, the authors present the results of a survey in the Netherlands where tissue samples and droppings were tested using a newly developed TaqMan PCR test for genotypic variation at codon 139 in the Vkorc1 gene associated with anticoagulant rodenticide r...

Coumarin oral anticoagulant drugs have proven to be effective for the prevention of thromboembolic events. World-wide, warfarin is the most prescribed drug. In Europe, acenocoumarol and phenprocoumon are also administered. Yet it has been proven that variant alleles of the VKORC1 and CYP2C9 genotypes influence the pharmacokinetics and pharmacodynamics of these drugs. The combination of these tw...

Coumarins are widely prescribed worldwide, and in Mexico acenocumarol is the preferred form. It is well known that despite its efficacy, coumarins show a high variability for dose requirements. We investigated the pharmacogenetic variation of 110 genes in patients receiving acenocumarol using a targeted NGS approach. We report relevant population differentiation for variants on CYP2C8, CYP2C19,...

Vitamin K 2,3-epoxide reductase complex subunit 1 (VKORC1) catalyses the reduction of vitamin K and its 2,3-epoxide essential to sustain γ-carboxylation of vitamin K-dependent proteins. Two different phenotypes are associated with mutations in human VKORC1. The majority of mutations cause resistance to 4-hydroxycoumarin- and indandione-based vitamin K antagonists (VKA) used in the prevention an...

Studies assessing the impact of gene-environment interactions on common human diseases and traits have been relatively few for many reasons. One often acknowledged reason is that it is difficult to accurately measure the environment or exposure. Indeed, most large-scale epidemiologic studies use questionnaires to assess and measure past and current exposure levels. While questionnaires may be c...

Since the discovery of warfarin-sensitive vitamin K 2,3-epoxide reductase complex subunit 1 (VKORC1), 26 human VKORC1 (hVKORC1) missense mutations have been associated with oral anticoagulant resistance (OACR). Assessment of warfarin resistance using the "classical" dithiothreitol-driven vitamin K 2,3-epoxide reductase (VKOR) assay has not reflected clinical resistance phenotypes for most mutat...