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, Rick A Kittles, A. Barbour, M. Tuck, S. D. McIntosh, J. N. Douglas, D. Nicolae, L. H. Cavallari, M. A. Perera

Research output: Contribution to journalArticle

45 Scopus citations

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 languageEnglish (US)
Pages (from-to)223-228
Number of pages6
JournalPharmacogenomics Journal
Volume14
Issue number3
DOIs
Publication statusPublished - 2014
Externally publishedYes

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Keywords

  • African Americans
  • algorithm
  • CYP2C9
  • polymorphisms
  • VKORC1
  • warfarin

ASJC Scopus subject areas

  • Pharmacology
  • Molecular Medicine
  • Genetics
  • Medicine(all)

Cite this

Hernandez, W., Gamazon, E. R., Aquino-Michaels, K., Patel, S., O'Brien, T. J., Harralson, A. F., ... 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