Ethnicity-specific pharmacogenetics: The case of warfarin in African Americans
Document Type
Journal Article
Publication Date
1-1-2014
Journal
Pharmacogenomics Journal
Volume
14
Issue
3
DOI
10.1038/tpj.2013.34
Keywords
African Americans; algorithm; CYP2C9; polymorphisms; VKORC1; warfarin
Abstract
Using a derivation cohort (N=349), we developed the first warfarin dosing algorithm that includes recently discovered polymorphisms in VKORC1 and CYP2C9 associated with warfarin dose requirement in African Americans (AAs). We tested our novel algorithm in an independent cohort of 129 AAs and compared the dose prediction to the International Warfarin Pharmacogenetics Consortium (IWPC) dosing algorithms. Our algorithm explains more of the phenotypic variation (R 2 =0.27) than the IWPC pharmacogenomics (R 2 =0.15) or clinical (R 2 =0.16) algorithms. Among high-dose patients, our algorithm predicted a higher proportion of patients within 20% of stable warfarin dose (45% vs 29% and 2% in the IWPC pharmacogenomics and clinical algorithms, respectively). In contrast to our novel algorithm, a significant inverse correlation between predicted dose and percent West African ancestry was observed for the IWPC pharmacogenomics algorithm among patients requiring ≥60 mg per week (β=-2.04, P=0.02). © 2014 Macmillan Publishers Limited.
APA Citation
Hernandez, W., Gamazon, E., Aquino-Michaels, K., Patel, S., O'Brien, T., Harralson, A., Kittles, R., Barbour, A., Tuck, M., McIntosh, S., Douglas, J., Nicolae, D., Cavallari, L., & Perera, M. (2014). Ethnicity-specific pharmacogenetics: The case of warfarin in African Americans. Pharmacogenomics Journal, 14 (3). http://dx.doi.org/10.1038/tpj.2013.34