ArticleEuropean journal of clinical pharmacology2010
Genetic determinants of acenocoumarol and phenprocoumon maintenance dose requirements.
Article in European journal of clinical pharmacology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 49 citations in OpenAlex.
- Quantifying the effect of covariates on concentrations and effects of steady-state phenprocoumon using a population pharmacokinetic/pharmacodynamic model.Clinical pharmacokinetics · 2013Trial
- Trial
- Prediction of phenprocoumon maintenance dose and phenprocoumon plasma concentration by genetic and non-genetic parameters.European journal of clinical pharmacology · 2011Trial
- Plant-derived coumarins: emerging natural scaffolds for antidiabetic drug discovery.Molecular diversity · 2026Review
- Influence of genetic and non-genetic factors on acenocoumarol maintenance dose requirement in a Tunisian population.European journal of clinical pharmacology · 2018Article
- Pharmacogenetic landscape of Metabolic Syndrome components drug response in Tunisia and comparison with worldwide populations.PloS one · 2018Article
- Genetic polymorphisms of pharmacogenomic VIP variants in the Uygur population from northwestern China.BMC genetics · 2015Article
- Pharmacogenetic-guided dosing of coumarin anticoagulants: algorithms for warfarin, acenocoumarol and phenprocoumon.British journal of clinical pharmacology · 2014Review
- An acenocoumarol dose algorithm based on a South-Eastern European population.European journal of clinical pharmacology · 2013Observational
- Does CALU SNP rs1043550 contribute variability to therapeutic warfarin dosing requirements?Clinical medicine & research · 2013Article
- An acenocoumarol dosing algorithm using clinical and pharmacogenetic data in Spanish patients with thromboembolic disease.PloS one · 2012Article
- Antithrombotic therapies in patients with prosthetic heart valves: guidelines translated for the clinician.Journal of thrombosis and thrombolysis · 2011Review
- Pharmacogenetics of anticoagulants.Human genomics and proteomics : HGP · 2010Article
- Pharmacogenetics aspects of oral anticoagulants therapy.Journal of medicine and lifeArticle
- A clinical conundrum: review of anticoagulation in pregnant women with mechanical prosthetic heart valves.Cardiovascular journal of AfricaReview
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectiveThe variability in warfarin dose requirement is attributable to genetic and environmental factors. Acenocoumarol (AC) and phenprocoumon (PC) are coumarin derivates widely prescribed in European countries for the prevention and treatment of thromboembolic events. The aim of our study was to investigate the contribution of genes involved in the vitamin K cycle to AC and PC maintenance doses.
methodsCommon single nucleotide polymorphisms (SNPs) in the genes encoding cytochrome P450 family member 2C9 (CYP2C9), vitamin K epoxide reductase complex subunit 1 (VKORC1), gamma-glutamyl carboxylase (GGCX), calumenin (CALU) and apolipoprotein E (APOE) were studied in 206 patients receiving AC or PC.
resultsCompared to patients with the VKORC1 C1173C genotype, maintenance doses for AC or PC were reduced to 74.6 or 70.2% in heterozygous C1173T subjects and to 48.6 or 48.1% in homozygous T1173T subjects (P < 0.0001). Furthermore maintenance doses for AC and PC were significantly lower in heterozygous CYP2C9*1*3, CYP2C9*2*3, and in CYP2C9*3*3 homozygote individuals compared to homozygous CYP2C9*1*1 subjects (P = 0.0004 and P = 0.0017, respectively). A multiple regression model including age, sex, last INR, VKORC1, and CYP2C9 genotypes explained ~50% of the variability in AC/PC dose requirements. CALU genotype combinations showed minor effects on PC dose requirements. No associations with AC or PC dose requirements were observed for sequence substitutions in the GGCX or APOE genes.
conclusionThese results reveal that interindividual variability in weekly AC and PC maintenance dose requirement is mainly dependent on the VKORC1 1173C>T and the CYP2C9*3 alleles. VKORC1 and CYP2C9 genotyping might provide helpful information to prevent serious bleeding events in subjects receiving AC or PC.
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