Ethnicity-specific pharmacogenetics: The case of warfarin in African Americans

W. Hernandez; E. R. Gamazon; K. Aquino-Michaels; S. Patel; T. J. O'Brien; A. F. Harralson; R. A. Kittles; A. Barbour; M. Tuck; S. D. McIntosh; J. N. Douglas; D. Nicolae; L. H. Cavallari; M. A. Perera

doi:10.1038/tpj.2013.34

Ethnicity-specific pharmacogenetics: The case of warfarin in African Americans

W. Hernandez, E. R. Gamazon, K. Aquino-Michaels, S. Patel, T. J. O'Brien, A. F. Harralson, R. A. Kittles, A. Barbour, M. Tuck, S. D. McIntosh, J. N. Douglas, D. Nicolae, L. H. Cavallari, M. A. Perera

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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).

Original language	English (US)
Pages (from-to)	223-228
Number of pages	6
Journal	Pharmacogenomics Journal
Volume	14
Issue number	3
DOIs	https://doi.org/10.1038/tpj.2013.34
State	Published - Jun 2014

Keywords

African Americans
CYP2C9
VKORC1
algorithm
polymorphisms
warfarin

ASJC Scopus subject areas

Molecular Medicine
Genetics
Pharmacology

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10.1038/tpj.2013.34

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Hernandez, W., Gamazon, E. R., Aquino-Michaels, K., Patel, S., O'Brien, T. J., Harralson, A. F., Kittles, R. A., Barbour, A., Tuck, M., McIntosh, S. D., Douglas, J. N., Nicolae, D., Cavallari, L. H., & Perera, M. A. (2014). Ethnicity-specific pharmacogenetics: The case of warfarin in African Americans. Pharmacogenomics Journal, 14(3), 223-228. https://doi.org/10.1038/tpj.2013.34

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title = "Ethnicity-specific pharmacogenetics: The case of warfarin in African Americans",

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).",

keywords = "African Americans, CYP2C9, VKORC1, algorithm, polymorphisms, warfarin",

author = "W. Hernandez and Gamazon, {E. R.} and K. Aquino-Michaels and S. Patel and O'Brien, {T. J.} and Harralson, {A. F.} and Kittles, {R. A.} and A. Barbour and M. Tuck and McIntosh, {S. D.} and Douglas, {J. N.} and D. Nicolae and Cavallari, {L. H.} and Perera, {M. A.}",

note = "Funding Information: This work was funded in part by the National Heart Lung and Blood Institute (K23 HL089808-01A2 to MAP), a grant from the American Heart Association Midwest Affiliate Grant-In-Aid (10GRNT3750024 to LHC) and by a grant from the National Collaborative on Aging (TJO).",

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AU - O'Brien, T. J.

AU - Harralson, A. F.

AU - Kittles, R. A.

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AU - McIntosh, S. D.

AU - Douglas, J. N.

AU - Nicolae, D.

AU - Cavallari, L. H.

AU - Perera, M. A.

N1 - Funding Information: This work was funded in part by the National Heart Lung and Blood Institute (K23 HL089808-01A2 to MAP), a grant from the American Heart Association Midwest Affiliate Grant-In-Aid (10GRNT3750024 to LHC) and by a grant from the National Collaborative on Aging (TJO).

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N2 - 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).

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Ethnicity-specific pharmacogenetics: The case of warfarin in African Americans

Abstract

Keywords

ASJC Scopus subject areas

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