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Factors influencing warfarin dose requirements in African-Americans
Kathryn M Momary1, Nancy L Shapiro, Marlos Ag Viana
1Mercer University College of Pharmacy, 3001 Mercer University Dr., Atlanta, GA, 30341-4155, USA. MOMARY_KM@Mercer.edu
Pharmacogenomics
|November 24, 2007
Summary
Genetic factors like CYP2C9 influence warfarin dose in African-Americans. Age and body size also impact dosage, while VKORC1 G6853C may not be a reliable predictor in this population.
Area of Science:
- Pharmacogenomics
- Genetics
- Internal Medicine
Background:
- African-Americans are underrepresented in warfarin pharmacogenetic studies.
- Understanding genetic contributors to warfarin response is crucial for personalized medicine.
Purpose of the Study:
- To investigate the association of CYP2C9, NQO1, and VKORC1 gene variants with warfarin dose requirements in African-Americans.
- To identify key genetic and clinical factors influencing warfarin dosing in this population.
Main Methods:
- Genotyping of CYP2C9 (*2, *3, *5), NQO1 (*2), and VKORC1 (G6853C) in 115 African-Americans on stable warfarin doses.
- Analysis of demographic and clinical data, including age and body surface area.
- Multiple regression analysis to determine factors associated with warfarin dose.
Main Results:
- CYP2C9 variants (*2, *3, *5) were associated with a significant reduction (38%) in warfarin dose.
- Neither NQO1 nor VKORC1 genotypes showed a significant association with warfarin dose in the overall population.
- CYP2C9 genotype, age, and body surface area jointly explained 33% of the variability in warfarin dose requirements.
Conclusions:
- CYP2C9 genotype, age, and body size are significant determinants of warfarin dose in African-Americans.
- The VKORC1 G6853C polymorphism alone may not be a reliable predictor of warfarin dose in this racial group.
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