Genetic Study of
Genetic Study of Warfarin
Evaluation of the genotypes that affect Warfarin metabolism.
The utility of genetic testing is recognized in guidelines related to the management of Warfarin therapeutics.
It is recommended for:
Warfarin Pharmacogenetics Test
What is evaluated in this test?
Our genetic test evaluates 3 genetic variants in CYP2C9 and VKORC1 genes associated with Warfarin’s pharmacokinetics and pharmacodynamics.
The CYP2C9 and VKORC1 genotype study can be used to determine the optimal starting dose of Warfarin.
It is scientifically established that several variants of CYP2C9 are associated with reduced enzyme activity and lower clearance rates of warfarin. The *2 and *3 alleles of CYP2C9 gene are responsible for a reduction in Warfarin metabolism.
By its turn, genetic variants in the VKORC1 gene cause a significant difference in Warfarin sensitivity index. The variant G-1639A in VKORC1 gene is a major determinant of variability in sensitivity to Warfarin.
These variants have been approved by the FDA and also by the International Warfarin Pharmacogenomics Consortium to guide therapy.
By evaluating CYP2C9 and VKORC1 genetic variants it is possible to evaluate the Warfarin metabolism and, as such, to prescribe an adequate dose to each individual.
Benefits of Study Warfarin Pharmacogenetics
Predict the optimal warfarin dose
A sample of blood or saliva is enough to perform the genetic test
Minimizes the risk for the major complication associated with warfarin. Overdosing can result in bleeding; underdosing can result in thrombosis
Optimized drug dose according to each patient genetic profile
Reduce patients morbidity and healthcare costs due to non-adequate Warfarin therapeutics
Evaluates all 18 possible haplotypes
1. Warfarin Intro
Warfarin efficacy is highly dependent on achieving and maintaining a narrow therapeutic window. Its use is associated with increased risk of blood clot formation when treatment is subtherapeutic (INR of less than 2) or bleeding when supratherapeutic (INR of 4 or more).
An increased warfarin levels is a reflection of patient overmedication and can account for increased bleeding incidents in some patients.
Clinical factors, demographic variables and variations in CYP2C9 and VKORC1 genes contribute significantly to the variability among patients in dose requirements for Warfarin.
2. Key Protein and genes
CYP2C9 – Cytochrome P450, Family , Subfamily C, Polypeptide 9
Is a member of the cytochrome P450 superfamily with a significant action in Warfarin metabolism.
VKORC1 – Vitamine K Epoxide Reductase Complex, Subunit 1
Encodes the Vitamin K-epoxide reductase, which catalyses the rate-limitin step in vitamin K recycling: the conversion of vitamin K-epoxide to vitamin K.
3. Warfarin genetic painel
The warfarin genetic test developed by HeartGenetics includes the evaluation of 2 genetics variants in CYP2C9 gene and 1 genetic variant in VKORC1 gene.
4. How Genetic variants are selected
Our research is supported by peer review papers that have been published in the reference journals in the field.
All genetic variants have been validated in reference databases (HGMDP, NCBI-OMIM, NCBI-ClinVar, NCBI-Variation Reporter, Ensembl and PharmGKB).
The knowledge in our databases was approved by internationally recognized medical geneticist and cardiologists.
5. International Guidelines
The FDA-approved warfarin drug label provides a dosing table based on CYP2C9 and VKORC1 genotypes.
Also, the Clinical Pharmacogenetics Implementation Consortium (CPIC) of the National Institutes of Health Pharmacogenomics Research Network develops peer-reviewed gene–drug guidelines that are published and updated periodically based on new developments in the field [2,9].
6. HeartGenetics’ Warfarin Pharmacogenetics reports
The Warfarin pharmacogenetics panel includes genetic variants associated with variability in Warfarin metabolism and the increased relative risk for bleeding or thrombosis.
The used technology has a 99% of accuracy.
All evidences are supported by updated scientific knowledge and validated by medical doctors.
All results include supporting information for each genetic variant including scientific references to guide the interpretation of test results.
HeartGenetics reports follow the recommendations from the European Society of Human Genetics
Contact us here for a report example.
 Food and Drug Administration webpage: http://www.fda.gov/
 Clin Pharmacol Ther. 2011. 90(4):625-9. Clinical Pharmacogenetics Implementation Consortium Guidelines for CYP2C9 and VKORC1 genotypes and warfarin dosing.
 Clin Cardiol. 2014. 37(1):48-56. Pharmacogenetics in cardiovascular disease: the challenge of moving from promise to realization: concepts discussed at the Canadian Network and Centre for Trials Internationally Network Conference (CANNeCTIN), June 2009.
 N Engl J Med. 2009. 360(8):753-64. Estimation of the warfarin dose with clinical and pharmacogenetic data.
 PLoS One. 2012. 7(8):e44064. Influence of CYP2C9 and VKORC1 on patient response to warfarin: a systematic review and meta-analysis.
 Mayo Clin Proc. 2009. 84(12):1079-94. Warfarin sensitivity genotyping: a review of the literature and summary of patient experience.
 Annu Rev Med. 2010. 61:63-75. Pharmacogenetics of warfarin.
 N Engl J Med. 2005. 352(22):2285-93. Effect of VKORC1 haplotypes on transcriptional regulation and warfarin dose.