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


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2014-06

AUTHORS

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

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). More... »

PAGES

223

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/tpj.2013.34

DOI

http://dx.doi.org/10.1038/tpj.2013.34

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1006146074

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/24018621


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