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

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

The pharmacogenomics journal, 2014-06, Vol.14 (3), p.223-228 [Periódico revisado por pares]

United States: Nature Publishing Group

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Título:
Ethnicity-specific pharmacogenetics: the case of warfarin in African Americans
Autor: 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
Assuntos: African Americans ; Algorithms ; Anticoagulants - pharmacokinetics ; Anticoagulants - therapeutic use ; Cohort Studies ; Cytochrome P-450 CYP2C9 - genetics ; Dosage ; Dosage and administration ; Drug metabolism ; Female ; Genetic aspects ; Genetic polymorphisms ; Humans ; Identification and classification ; Male ; Patients ; Pharmacogenetics ; Pharmacogenomics ; Phenotypic variations ; Vitamin K Epoxide Reductases - genetics ; Warfarin ; Warfarin - pharmacokinetics ; Warfarin - therapeutic use
É parte de: The pharmacogenomics journal, 2014-06, Vol.14 (3), p.223-228
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SourceType-Scholarly Journals-1
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Descrição: 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).
Editor: United States: Nature Publishing Group
Idioma: Inglês

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

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

United States: Nature Publishing Group

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