Abstract
The identification of the genes encoding CYP2C9, the principal metabolizing enzyme of the coumarins, and VKORC1, the molecular target for coumarins, has strongly stimulated the research on pharmacogenetics of vitamin K antagonists, also designated as coumarins. From 1999 to 2004 a number of observational studies firmly established associations between being carrier of the CYP2C9*2 and especially the CYP2C9*3 allele and reduced coumarin dose requirements and increased risks of overanticoagulation and even major bleeding compared to CYP2C9 wild type patients. The identification of the VKORC1 gene in 2004 gave rise to more observational studies, which mostly indicated a larger contribution of variants of these gene to the interindividual variability in dose requirements. However, whereas overanticoagulation in the initial period of therapy appears to be associated with VKORC1 as well as CYP2C9 genotype, the CYP2C9 genotype could be a more important predictor for major bleeding and retarded stabilisation. The recent discovery that only one single nucleotide polymorphism in the VKORC1 gene, the -1639G > A polymorphism, is representative for VKORC1 activity and the recent conclusion from a genome-wide scan that VKORC1 and CYP2C9 are the only genes with relevant effects on coumarin response, seem to be definitive demarcations of the genetic information which could be needed for improvement of the existing coumarin dosing algorithms. The observational studies from the last decade provided valuable insights into the effects of genetic factors on variability in coumarin response. During the forthcoming years randomized clinical trials are needed to evaluate whether this genetic information will improve the benefit-risk ratio of coumarins.
Current Pharmaceutical Design
Title: Pharmacogenetics of Oral Anticoagulant Therapy
Volume: 16 Issue: 2
Author(s): T. Schalekamp and A. de Boer
Affiliation:
Abstract: The identification of the genes encoding CYP2C9, the principal metabolizing enzyme of the coumarins, and VKORC1, the molecular target for coumarins, has strongly stimulated the research on pharmacogenetics of vitamin K antagonists, also designated as coumarins. From 1999 to 2004 a number of observational studies firmly established associations between being carrier of the CYP2C9*2 and especially the CYP2C9*3 allele and reduced coumarin dose requirements and increased risks of overanticoagulation and even major bleeding compared to CYP2C9 wild type patients. The identification of the VKORC1 gene in 2004 gave rise to more observational studies, which mostly indicated a larger contribution of variants of these gene to the interindividual variability in dose requirements. However, whereas overanticoagulation in the initial period of therapy appears to be associated with VKORC1 as well as CYP2C9 genotype, the CYP2C9 genotype could be a more important predictor for major bleeding and retarded stabilisation. The recent discovery that only one single nucleotide polymorphism in the VKORC1 gene, the -1639G > A polymorphism, is representative for VKORC1 activity and the recent conclusion from a genome-wide scan that VKORC1 and CYP2C9 are the only genes with relevant effects on coumarin response, seem to be definitive demarcations of the genetic information which could be needed for improvement of the existing coumarin dosing algorithms. The observational studies from the last decade provided valuable insights into the effects of genetic factors on variability in coumarin response. During the forthcoming years randomized clinical trials are needed to evaluate whether this genetic information will improve the benefit-risk ratio of coumarins.
Export Options
About this article
Cite this article as:
Schalekamp T. and de Boer A., Pharmacogenetics of Oral Anticoagulant Therapy, Current Pharmaceutical Design 2010; 16 (2) . https://dx.doi.org/10.2174/138161210790112737
DOI https://dx.doi.org/10.2174/138161210790112737 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
Call for Papers in Thematic Issues
"Tuberculosis Prevention, Diagnosis and Drug Discovery"
The Nobel Prize-winning discoveries of Mycobacterium tuberculosis and streptomycin have enabled an appropriate diagnosis and an effective treatment of tuberculosis (TB). Since then, many newer diagnosis methods and drugs have been saving millions of lives. Despite advances in the past, TB is still a leading cause of infectious disease mortality ...read more
Current Pharmaceutical challenges in the treatment and diagnosis of neurological dysfunctions
Neurological dysfunctions (MND, ALS, MS, PD, AD, HD, ALS, Autism, OCD etc..) present significant challenges in both diagnosis and treatment, often necessitating innovative approaches and therapeutic interventions. This thematic issue aims to explore the current pharmaceutical landscape surrounding neurological disorders, shedding light on the challenges faced by researchers, clinicians, and ...read more
Emerging and re-emerging diseases
Faced with a possible endemic situation of COVID-19, the world has experienced two important phenomena, the emergence of new infectious diseases and/or the resurgence of previously eradicated infectious diseases. Furthermore, the geographic distribution of such diseases has also undergone changes. This context, in turn, may have a strong relationship with ...read more
Melanoma and Non-Melanoma Skin Cancer Treatment: Standard of Care and Recent Advances
In this thematic issue, we aim to provide a standard of care of the diagnosis and treatment of melanoma and non-melanoma skin cancer. The editor will invite authors from different countries who will write review articles of melanoma and non-melanoma skin cancers. The Diagnosis, Staging, Surgical Treatment, Non-Surgical Treatment all ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
Methylglyoxal and Advanced Glycation Endproducts: New Therapeutic Horizons?
Recent Patents on Cardiovascular Drug Discovery Stem Cell Regenerative Potential Combined with Nanotechnology and Tissue Engineering for Myocardial Regeneration
Current Stem Cell Research & Therapy Recent Advances in the Treatment of Neurogenic Erectile Dysfunction
Recent Patents on CNS Drug Discovery (Discontinued) Amyloid A Amyloidosis Secondary to Rheumatoid Arthritis: An Uncommon Yet Important Complication
Current Rheumatology Reviews Targeting the EGF/HER Ligand-Receptor System in Cancer
Current Pharmaceutical Design Enediyne Anticancer Antibiotic Lidamycin: Chemistry, Biology and Pharmacology
Anti-Cancer Agents in Medicinal Chemistry It’s Time for An Epigenomics Roadmap of Heart Failure
Current Genomics Link between Metabolic Syndrome and Insulin Resistance
Current Vascular Pharmacology Sealing the Broken Barrier in IBD: Intestinal Permeability, Epithelial Cells and Junctions
Current Drug Targets Effect of Non-Statin Lipid Lowering and Anti-Obesity Drugs on LDL Subfractions in Patients with Mixed Dyslipidaemia
Current Vascular Pharmacology Mesenchymal Stromal Cells: A Promising Cell Source for the Treatment of Inflammatory Cardiomyopathy
Current Pharmaceutical Design Glycoxidation and Wound Healing in Diabetes: An Interesting Relationship
Current Diabetes Reviews EGFR and the Complexity of Receptor Crosstalk in the Cardiovascular System
Current Molecular Medicine COX-2 Inhibitors and Cardiovascular Events: Deja Vu Du Jour
Vascular Disease Prevention (Discontinued) Identification of Prognostic Biomarkers in Papillary Thyroid Cancer and Developing Non-Invasive Diagnostic Models Through Integrated Bioinformatics Analysis
MicroRNA Cardiac MRI in Infiltrative Disorders: A Concise Review
Current Cardiology Reviews Modulation of Collagen Turnover in Cardiovascular Disease
Current Pharmaceutical Design Resuscitation of the Patient with the Functionally Univentricular Heart
Current Pediatric Reviews <i>Circular RNA NF1-419</i> Inhibits Proliferation and Induces Apoptosis by Regulating Lipid Metabolism in Astroglioma Cells
Recent Patents on Anti-Cancer Drug Discovery Use of Recombinant Human Erythropoietin as an Antianemic and Performance Enhancing Drug
Current Pharmaceutical Biotechnology