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

Hernandez W, Gamazon ER, Aquino-Michaels K, Patel S, O'Brien TJ, Harralson AF, Kittles RA, Barbour A, Tuck M, McIntosh SD, Douglas JN, Nicolae D, Cavallari LH, Perera MA
Pharmacogenomics J. 2014 14 (3): 223-8

PMID: 24018621 · PMCID: PMC4016191 · DOI:10.1038/tpj.2013.34

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).

MeSH Terms (9)

Anticoagulants Cohort Studies Cytochrome P-450 CYP2C9 Female Humans Male Pharmacogenetics Vitamin K Epoxide Reductases Warfarin

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