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PLoS One. 2016 Jan 8;11(1):e0145480. doi: 10.1371/journal.pone.0145480. eCollection 2016.

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

Author information

1
Pharmaceutical Sciences Department, School of Pharmacy, University of Puerto Rico Medical Sciences Campus (UPR-MSC), San Juan, Puerto Rico, United States of America.
2
Department of Pharmacology and Toxicology, School of Medicine, University of Puerto Rico Medical Sciences Campus (UPR-MSC), San Juan, Puerto Rico, United States of America.
3
Pharmacy Service, VA Caribbean Healthcare Systems (VACHS), San Juan, Puerto Rico, United States of America.
4
Molecular Genetics Lab, Department of Biochemistry, School of Medicine, University of Puerto Rico Medical Sciences Campus (UPR-MSC), San Juan, Puerto Rico, United States of America.
5
Brownstone Outpatient Clinic, Hartford Hospital, Hartford, CT, United States of America.
6
Genomas Inc., Hartford, CT, United States of America.

Abstract

AIM:

This study is aimed at developing a novel admixture-adjusted pharmacogenomic approach to individually refine warfarin dosing in Caribbean Hispanic patients.

PATIENTS & METHODS:

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.

RESULTS:

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<0.001). The admixture-driven pharmacogenetic algorithm predicted 58% of warfarin dose variance when externally validated in 55 individuals from an independent validation cohort (MAE = 0.89 mg/day, 24% mean bias).

CONCLUSIONS:

Results supported our rationale to incorporate individual's genotypes and unique admixture metrics into pharmacogenetic refinement models in order to increase predictability when expanding them to admixed populations like Caribbean Hispanics.

TRIAL REGISTRATION:

ClinicalTrials.gov NCT01318057.

PMID:
26745506
PMCID:
PMC4706412
DOI:
10.1371/journal.pone.0145480
[Indexed for MEDLINE]
Free PMC Article

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