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Published on: April 1, 2019
Dosing algorithm for warfarin using CYP2C9 and VKORC1 genotyping from a multi-ethnic population: comparison with
Alan H B Wu1, Ping Wang, Andrew Smith
1University of California, Department of Laboratory Medicine, Clinical Chemistry Laboratory, San Francisco General Hospital, 1001 Potrero Ave., San Francisco, CA 94110, USA. wualan@labmed2.ucsf.edu
Pharmacogenomics
|March 29, 2008
Summary
Genetic variations in CYP2C9 and VKORC1 influence warfarin dosing. A new algorithm incorporating ethnicity and specific gene variants showed minor improvements for stable anticoagulation in a multi-ethnic population.
Area of Science:
- Pharmacogenomics
- Drug Metabolism
- Genetics
Background:
- Cytochrome P450 2C9 (CYP2C9) and vitamin K epoxide reductase complex subunit 1 (VKORC1) gene polymorphisms significantly impact warfarin pharmacokinetics and pharmacodynamics.
- Accurate warfarin dosing is crucial for achieving therapeutic anticoagulation and minimizing bleeding risks.
Purpose of the Study:
- To develop and validate a warfarin-dosing algorithm tailored for a multi-ethnic population.
- To compare the performance of the developed algorithm against existing warfarin-dosing regression equations.
Main Methods:
- Determined allele and haplotype frequencies of CYP2C9 and VKORC1 in 167 Caucasian, African-American, Asian, and Hispanic patients on warfarin.
- Developed a dosing equation using demographic variables and genotypes on a subset of 92 patients.
- Validated the regression model against an independent group and compared it with five other published equations.
Main Results:
- Allele frequencies for CYP2C9*2, CYP2C9*3, and VKORC1 3673 were consistent with previous reports.
- The developed linear regression model achieved r-values of 0.71 (training) and 0.67 (validation), improving to 0.78 and 0.75 with rare genotype exclusion or VKORC1 7566 genotype inclusion.
- Excluding ethnicity-associated rare genotypes enhanced model performance.
Conclusions:
- Incorporating ethnicity and additional CYP2C9 and VKORC1 single nucleotide polymorphisms (SNPs) offers minor improvements to warfarin-dosing algorithms.
- Significant advancements in warfarin dosing precision likely necessitate the discovery of novel gene associations.
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