A Novel Admixture-Based Pharmacogenetic Approach to Refine Warfarin Dosing in Caribbean Hispanics

This study is aimed at developing a novel admixture-adjusted pharmacogenomic approach to individually refine warfarin dosing in Caribbean Hispanic patients. A multiple linear regression analysis of effective warfarin doses versus relevant genotypes, admixture, clinical and demographic factors was pe...

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Veröffentlicht in:PloS one 2016-01, Vol.11 (1), p.e0145480
Hauptverfasser: Duconge, Jorge, Ramos, Alga S, Claudio-Campos, Karla, Rivera-Miranda, Giselle, Bermúdez-Bosch, Luis, Renta, Jessicca Y, Cadilla, Carmen L, Cruz, Iadelisse, Feliu, Juan F, Vergara, Cunegundo, Ruaño, Gualberto
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Sprache:eng
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Zusammenfassung:This study is aimed at developing a novel admixture-adjusted pharmacogenomic approach to individually refine warfarin dosing in Caribbean Hispanic patients. A multiple linear regression analysis of effective warfarin doses versus relevant genotypes, admixture, clinical and demographic factors was performed in 255 patients and further validated externally in another cohort of 55 individuals. The admixture-adjusted, genotype-guided warfarin dosing refinement algorithm developed in Caribbean Hispanics showed better predictability (R2 = 0.70, MAE = 0.72mg/day) than a clinical algorithm that excluded genotypes and admixture (R2 = 0.60, MAE = 0.99mg/day), and outperformed two prior pharmacogenetic algorithms in predicting effective dose in this population. For patients at the highest risk of adverse events, 45.5% of the dose predictions using the developed pharmacogenetic model resulted in ideal dose as compared with only 29% when using the clinical non-genetic algorithm (p
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0145480